Dose Of Capsules Research Articles

Effect of N-Acetylcysteine on IL-10 and Total Lymphocyte Count in HIV Infected Patients Undergoing Antiretroviral Treatment

Objective: To determine NAC oral administration’s effect on changes in IL-10 levels and total lymphocyte count (TLC) in patients with HIV/AIDS in Dr Mohammad Hoesin Hospital, Palembang. Material and Methods: This study was a double-blind, randomized clinical trial. A total of 32 HIV/AIDS patients undergoing ARV treatment were randomly divided into two groups: the placebo and NAC groups. In the placebo group, patients were given capsules containing lactose at a dose of 3x1 capsules/ day, while the NAC group, were given NAC at a dose of 3x200 mg/day. Each group was treated for 12 weeks. Results: NAC administration significantly reduced IL-10 levels P= 0.038 but could not significantly increase TLC after treatment P= 0.376. However, TLC on the NAC group remained higher when compared with TLC on the placebo group. Conclusion: NAC administration significantly reduced levels of IL-10 and increased TLC; therefore, NAC has potential effects of increasing the effectiveness of antiretroviral therapy in HIV/AIDS patients, although it still needs to be studied further. J MEDICINE 2021; 22: 114-118

Treatment of Idiopathic Pulmonary Fibrosis with Capsule or Tablet Formulations of Pirfenidone in the Real-Life French RaDiCo-ILD Cohort.

Pirfenidone, an antifibrotic medication for idiopathic pulmonary fibrosis (IPF), is now available in France in two formulations: tablets since April 2018, and the initial capsules form. We conducted a cohort study to describe tolerance and acceptability of capsules and/or tablets of pirfenidone in patients with IPF. This study was nested within the French, non-randomized, multicenter RaDiCo-ILD (Rare Disease Cohort-Interstitial Lung Diseases). Included patients with IPF received at least one dose of pirfenidone tablets or capsules from July 2017 to June 2019 in three populations: the inclusion population (patients treated at least once with pirfenidone during the study period, n = 288); the potential switch population (patients treated with pirfenidone during the switch period starting April 2018, n = 256); the newly treated population (patients who initiated pirfenidone during the study period, n = 162). Each of those last two populations included three subgroups (tablets, capsules, and substitution). In 288 patients treated, 162 newly initiated pirfenidone during the study period: there were no meaningful differences in the baseline characteristics with the 256 patients treated during the potential switch period. In the newly treated population, 30.3% started pirfenidone treatment with tablet formulation. In the potential switch population, 44.9% of patients shifted from capsule to tablet. Half of the patients shifted to tablet formulation within the first 10months. The mean treatment duration was 21.5months with a mean dose of 2106.7mg/day; 46.5% of patients discontinued treatment, mainly because of adverse events. There were fewer discontinuations in the tablets and substitution subgroups than in the capsules-only subgroup. The most reported adverse event was skin rash (11.5%). No new adverse event was identified. This real-life cohort assessing the characteristics of the prescription of pirfenidone tablets and capsules suggests a good acceptability of the tablet formulation by patients with IPF. Clinical trial registered with www.clinicaltrials.gov (NCT04238871).

Comparison between planar and single-photon computed tomography images for radiation intensity quantification in iodine-131 scintigraphy

This study aimed to evaluate the feasibility of quantifying iodine-131 (131I) accumulation in scintigraphy images and compare planar and single-photon emission computed tomography (SPECT) images to estimate 131I radioactivity in patients receiving radioactive iodine therapy for thyroid cancer. We evaluated 72 sets of planar and SPECT images acquired between February 2017 and December 2018. Simultaneously, we placed a reference 131I capsule next to the patient during image acquisition. We evaluated the correlation between the intensity of the capsule in the images and the capsule dose and estimated the radiation dose at the thyroid bed. The mean capsule dose was 2.14 MBq (range, 0.63–4.31 MBq). The correlation coefficients (p-value) between capsule dose and maximum and mean intensities in both planar and SPECT images were 0.93 (p < 0.01), 0.96 (p < 0.01), 0.60 (p < 0.01), and 0.47 (p < 0.01), respectively. The mean intensities of planar images show the highest correlation coefficients. Based on a regression equation, the average radiation dose in the thyroid bed was 5.9 MBq. In conclusion, planar images reflected the radiation dose more accurately than SPECT images. The regression equation allows to determine the dose in other regions, such as the thyroid bed or sites of distant metastasis.

PK and PD Assessment of BET Inhibitor Pelabresib (CPI-0610) in Patients with Relapsed or Refractory Lymphoma: Findings from a Phase 1 Study

PK and PD Assessment of BET Inhibitor Pelabresib (CPI-0610) in Patients with Relapsed or Refractory Lymphoma: Findings from a Phase 1 Study

Inhibition test of mangosteen peel extract (Garcinia mangostana L.) against bacterial diseases of tiger grouper (Epinephellus fuscoguttatus)

Cultivation of tiger grouper (Epinephelus fuscoguttatus) in Floating Net Cages in several locations in Bireuen Regency has developed. The potential disease issue can be caused by bacteria, viruses, fungi, or parasites. The purpose of this study was to determine the effectiveness of mangosteen peel extract capsules (Garcinia mangostana L) against bacterial disease in tiger grouper. This research was carried out in April 2019 at the MIPA Laboratory of Al Muslim University and the laboratory of PT. Centra Proteina Prima, Bireuen Regency. The design used was a completely randomized design with four treatments (0%, 10%, 20%, and 30% mangosteen peel extract capsules) with three replications. The parameters studied in this study including the diameter of the inhibition and the observation of MBC (Minimum Bacterial Concentration). The result showed that the administration of mangosteen peel extract capsules with doses of 10%, 20%, and 30% has no significant effect on reducing disease-causing bacteria in grouper grown on TSA media. Positive results were obtained on positive (+) MBC observations, presumably due to the small dose of mangosteen peel extract capsules given so that it could not kill bacteria grown in dishes with an inhibition range of 0 mm.Introduction

Physiologically Based Biopharmaceutics Modeling to Demonstrate Virtual Bioequivalence and Bioequivalence Safe-space for Ribociclib which has Permeation Rate-controlled Absorption

A physiologically based biopharmaceutics model (PBBM) was developed to support formulation development of ribociclib, an orally bioavailable selective CDK4/6 inhibitor. Ribociclib is a weak base with moderate permeability and complete in vitro dissolution under stomach pH. GastroPlus™ was used to simulate the pharmacokinetics (PK) in healthy volunteers after capsule dosing. Simulations showed rapid, complete dissolution in human stomach without intestinal precipitation and with permeation-controlled absorption. Permeability was identified as controlling the systemic exposure. PBBM predicted bioequivalence (BE) between capsule and tablet in healthy volunteers, despite non-similarity between in vitro dissolution kinetics (f2<50). BE was verified in a clinical study. Then virtual bioequivalence (VBE) simulations predicted comparable PK in cancer patients between capsule and tablet of commercial batch, which was also confirmed in a clinical study. Finally, virtual trial simulations using virtual batches with slower dissolution were used to define an in vitro BE safe-space for tablets, where BE is expected. PBBM can identify drugs with permeability-controlled absorption for which formulation optimization can focus more on manufacturability rather than dissolution. PBBM can be used to predict BE study outcomes, define clinically relevant specification and BE safe-space, superseding dissolution similarity f2 criteria.

Wuzhi Capsule Dosage Affects Tacrolimus Elimination in Adult Kidney Transplant Recipients, as Determined by a Population Pharmacokinetics Analysis.

PurposeIn this study, we aimed to establish a tacrolimus population pharmacokinetic model and better understand the drug-drug interaction between Wuzhi capsule and tacrolimus in Chinese renal transplant recipients.Patients and MethodsWe performed a population pharmacokinetic analysis using a non-linear mixed-effects model to determine the suitable Wuzhi capsule dose in combination with tacrolimus. Data on 1378 tacrolimus steady-state concentrations were obtained from 142 patients who received kidney transplant in Changhai Hospital and Huashan Hospital. Demographic characteristics, laboratory tests, genetic polymorphisms, and co-medications were evaluated.ResultsThe one-compartment model best described data. Our final model identified creatinine clearance rate, hematocrit, Wuzhi capsule dose, CYP3A5*3 genetic polymorphisms, and tacrolimus daily dose as significant covariates for tacrolimus clearance, with the value of 14.4 L h−1, and the between-subject variability (BSV) was 25.4%. The Wuzhi capsule showed a dose-dependent effect on tacrolimus pharmacokinetics, demonstrating a stronger inhibitory effect than inductive effect.ConclusionOur model can accurately describe population pharmacokinetics of tacrolimus when combined with different doses of Wuzhi capsule. Additionally, this model can be used for individualizing tacrolimus dose following kidney transplantation.

Comparison of the effect of Ceratonia siliqua L. fruit oral capsule and vitamin E on semen parameters in men with idiopathic infertility: a triple-blind randomized controlled clinical trial.

To compare the effect of oral Ceratonia siliqua (Carob) and vitamin E on sperm parameters in idiopathic infertile men. In this triple-blind randomized controlled trial study, fifty 20-45-year-old infertile men with idiopathic abnormal sperm parameters were selected among men referring to the infertility clinic of Al Zahra-Iran Hospital, and randomly allocated into two groups. The first group received Carob capsules, 500mg, and the second group received vitamin E capsules three times a day for 90days. The primary outcomes of this study were the sperm parameters (count, motility, and morphology). After the intervention, the mean of sperm count increased from 49.08 to 60.22 million/mL in the carob vs. it increased from 47.64 to 58.88 million/mL in the vitamin E group (adjusted mean difference (aMD)=1.124 million/ml, 95% CI:-12.892 to 15.141). The mean sperm motility increased from 45.90 to 52.90% in the carob group but decreased from 55.23 to 38.10% in the vitamin E group (aMD=17.22%, 95% CI: 8.53 to 25.92). The mean sperms with normal morphology increased from 11.52 to 67.05% in the carob, and from 10.20 to 77.47% in the vitamin E group (aMD=-10.88%, 95% CI:-22.30 to 0.536). There was no serious side effect during the treatment course. Taking 1,500mg oral dose of Carob capsule per day for 90days improved sperm motility but had no significant effect for improving morphology and count comparing to vitamin E capsule.

Safety, Pharmacokinetics, Pharmacodynamics, and Formulation of Liver‐Distributed Farnesoid X‐Receptor Agonist TERN‐101 in Healthy Volunteers

TERN-101 is a nonsteroidal farnesoid X-receptor agonist being developed for the treatment of nonalcoholic steatohepatitis (NASH). We assessed the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of TERN-101 capsule and tablet formulations in healthy volunteers. In a randomized, double-blind, placebo-controlled study, 38 participants were enrolled and randomized to receive placebo or 25-, 75-, or 150-mg TERN-101 capsules orally once daily for 7 days. In a separate open-label PK and formulation-bridging study, 16 participants received single doses of TERN-101 tablets (5 and 25 mg) or capsules (25 mg). TERN-101 was overall well-tolerated in this healthy volunteer population; no pruritus was reported. TERN-101 capsule administration over 7 days resulted in decreases in serum 7α-hydroxy-4-cholesten-3-one that were sustained for 24 hours after the last dose (maximum suppression 91% from baseline), indicating target engagement in the liver. TERN-101 capsules exhibited less than dose-proportional PK. Relative to capsules, TERN-101 tablets showed increased bioavailability, with 24-hour plasma exposure of the 5-mg tablet similar to that of the 25-mg capsule. There was no significant effect of food on exposure. The overall safety, PK, and PD profiles of TERN-101 support its further evaluation for the treatment of NASH.

Vitamin D Perspective in Front Line Healthcare Workers Amid COVID-19

Deficiency of Vitamin D is very common in Pakistan, even among healthy asymptomatic individuals [1], [2]. Recent studies have shown that the risk of contracting COVID-19 was increased to two-fold, and consequent mortality to 4-fold if the person is Vitamin D deficient [3]. Health care workers including the nursing and administration staff are at a high risk of contracting SARS-CoV2 due to increased regular exposure in a health care setting [4]. Consequently, a convergence of the COVID-19 pandemic, the deficiency of Vitamin D, and the increased exposure can render the health care workers at an additional risk to COVID-19 infection. Our objective was to determine the prevalence of vitamin D deficiency in healthy asymptomatic front-line health care workers and to analyze the change in serum level by loading oral dose of SunnyD STAT softgel capsules (200000 IU Vitamin D3). We followed single centered, cross-sectional, cohort study with subsequent randomized placebo-controlled design for supplementation and follow up. Serum level of 25-hydroxyvitamin D (25OHD) was the main outcome variable, with anthropometric data, nutritional intake, and lifestyle variables analyzed for potential association as risk factors for the outcome. Severe Vitamin D deficiency was found to be prevalent among front line health care workers in this urban hospital-based sample. Serum level of Vitamin D was found to be significantly associated with designation and presence of high blood pressure. The likelihood of increased serum Vitamin D levels was observed with increasing monthly income, higher designation, increasing age and supplementation intake. Mean increase in the serum 25(OH)D3 level after 2 doses of SunnyD STAT softgel capsule (200000 IU Vitamin D3) was 34.22 ng/ml. Public health interventions regarding Vitamin D supplementation and awareness are needed, especially amid COVID-19 pandemicDeficiency of Vitamin D is very common in Pakistan, even among healthy asymptomatic individuals [1], [2]. Recent studies have shown that the risk of contracting COVID-19 was increased to two-fold, and consequent mortality to 4-fold if the person is Vitamin D deficient [3]. Health care workers including the nursing and administration staff are at a high risk of contracting SARS-CoV2 due to increased regular exposure in a health care setting [4]. Consequently, a convergence of the COVID-19 pandemic, the deficiency of Vitamin D, and the increased exposure can render the health care workers at an additional risk to COVID-19 infection. Our objective was to determine the prevalence of vitamin D deficiency in healthy asymptomatic front-line health care workers and to analyze the change in serum level by loading oral dose of SunnyD STAT softgel capsules (200000 IU Vitamin D3). We followed single centered, cross-sectional, cohort study with subsequent randomized placebo-controlled design for supplementation and follow up. Serum level of 25-hydroxyvitamin D (25OHD) was the main outcome variable, with anthropometric data, nutritional intake, and lifestyle variables analyzed for potential association as risk factors for the outcome. Severe Vitamin D deficiency was found to be prevalent among front line health care workers in this urban hospital-based sample. Serum level of Vitamin D was found to be significantly associated with designation and presence of high blood pressure. The likelihood of increased serum Vitamin D levels was observed with increasing monthly income, higher designation, increasing age and supplementation intake. Mean increase in the serum 25(OH)D3 level after 2 doses of SunnyD STAT softgel capsule (200000 IU Vitamin D3) was 34.22 ng/ml. Public health interventions regarding Vitamin D supplementation and awareness are needed, especially amid COVID-19 pandemic.

Histopathological nephrotoxic features of high oral doses of ubiquinone in rats

Abstract Co-enzyme Q10 (Co-Q10) plays a key role in the cellular respiration for the production of ATP. The toxicity of quinones to the kidney appears to depend on variety of factors, including genetic polymorphisms and the individual’s comorbidites. The aim of the present study was to assess histologically the nephrotoxic effects of 6 weeks daily oral intake of Co-Q10 in experimental animals. Twenty-five Wistar rats weighing between 220-270 g were randomly divided into two groups: experimental “treated” and control “untreated” groups (n=15, n=10, respectively). The animals of the experimental group received 300 mg/kg daily dose of gelatinous capsules of Co-Q10 by oral gavage for six weeks. At the end of the study, all animals were sacrificed under general anesthesia and samples of the kidneys were excised for microscopic histopathological assessment of renal tissue using stain. The experimental group showed a range of mild to severe dilatation of Bowman’s space, with a mean corpuscular diameter of 294±38 µm that was significantly higher (p &lt;0.05) than that of the untreated control group 208±31 µm. Shrinkage to complete destruction of the glomeruli was observed in the experimental group only. The long-term use of high doses of Co-Q10 had revealed a selective nephrotoxicity towards podocytes. This might be a risk factor leading to renal proximal tubular necrosis in rats and the subsequent renal function deterioration.

Luminal Bioavailability of Orally Administered ω-3 PUFAs in the Distal Small Intestine, and Associated Changes to the Ileal Microbiome, in Humans with a Temporary Ileostomy.

ABSTRACTBackgroundOral administration of purified omega-3 (ω-3) PUFAs is associated with changes to the fecal microbiome. However, it is not known whether this effect is associated with increased PUFA concentrations in the gut.ObjectivesWe investigated the luminal bioavailability of oral ω-3 PUFAs (daily dose 1 g EPA and 1g DHA free fatty acid equivalents as triglycerides in soft-gel capsules, twice daily) and changes to the gut microbiome, in the ileum.MethodsIleostomy fluid (IF) and blood were obtained at baseline, after first capsule dosing (median 2 h), and at a similar time after final dosing on day 28, in 11 individuals (median age 63 y) with a temporary ileostomy. Fatty acids were measured by LC–tandem MS. The ileal microbiome was characterized by 16S rRNA PCR and Illumina sequencing.ResultsThere was a mean 6.0 ± 9.8-fold and 6.6 ± 9.6-fold increase in ileal EPA and DHA concentrations (primary outcome), respectively, at 28 d, which was associated with increased RBC ω-3 PUFA content (P ≤ 0.05). The first oral dose did not increase the ileal ω-3 PUFA concentration except in 4 individuals, who displayed high luminal EPA and DHA concentrations, which reduced to concentrations similar to the overall study population at day 28, suggesting physiological adaptation. Bacteroides, Clostridium, and Streptococcus were abundant bacterial genera in the ileum. Ileal microbiome variability over time and between individuals was large, with no consistent change associated with acute ω-3 PUFA dosing. However, high concentrations of EPA and DHA in IF on day 28 were associated with higher abundance of Bacteroides (r2 > 0.86, P < 0.05) and reduced abundance of other genera, including Actinomyces (r2 > 0.94, P < 0.05).ConclusionsOral administration of ω-3 PUFAs leads to increased luminal ω-3 PUFA concentrations and changes to the microbiome, in the ileum of individuals with a temporary ileostomy. This study is registered on the ISRCTN registry as ISRCTN14530452.

Acute Ingestion of Montmorency Tart Cherry Reduces Serum Uric Acid but Has no Impact on High Sensitivity C-Reactive Protein or Oxidative Capacity.

Tart cherries are particularly high in anthocyanins and are believed to have many health benefits, including reducing inflammation and oxidative stress. However, comparison between dosages and formulations are lacking. Forty-eight participants were randomly allocated to one of six experimental treatment groups where they ingested tart cherry or placebo in either juice (240ml per bottle) or powdered capsule form (480mg per capsule) once or twice daily for 48h and markers of inflammation (uric acid (UA), high-sensitivity C-reactive protein (hsCRP)) and oxidative capacity (plasma oxygen radical absorbance capacity (ORAC)) were measured. There was a group x time interaction for UA (p= 0.02), which declined up to 24h post ingestion for a single capsule dose, up to 8h for a two capsule dose, and up to 2h for a single juice dose. There was an increase in UA from 8h until 48h post ingestion in a single juice dose. Overall, there was an average 8% decrease in UA. There was no significant change over time in hsCRP (p= 0.64) or ORAC (p= 0.42) or between groups in hsCRP (p= 0.47) or ORAC (p= 0.21). Our data indicates tart cherry ingestion can transiently decrease UA and not maintained with continued supplementation. Additionally, there were differences in formulations and doses indicating a single powdered capsule is most effective for lowering UA suggesting capsules may be used by those who do not enjoy the taste of tart cherry juice. This study was registered at ClinicalTrials.gov , NCT04497077, 7/29/2020, retrospectively registered.

Comparing the effects of saffron, lippia, and saffron-lippia combination on anxiety among candidates for coronary angiography.

Objective:Coronary artery disease (CAD) is among the most prevalent diseases in the world, and its severity is usually assessed through coronary angiography (CA). Anxiety is the most prevalent problem before angiography. The aim of this study was to evaluate Crocus sativus (saffron) and Lippia citriodora Kunth (lippia) extracts and saffron-lippia extract combination on anxiety among the candidates for CA. Materials and Methods:This double-blind randomized placebo-controlled trial in four month was conducted on 120 angiography candidates in Valiasr hospital, Birjand, Iran. The random allocation was doing through block randomization to saffron, lippia, saffron-lippia, and placebo groups; four hours before angiography, participants in these groups respectively received a single dose of saffron extract capsule (40 mg), lippia extract capsule (40 mg), saffron-lippia extract capsule (20 mg saffron and 20 mg lippia), and lactulose capsule (40 mg). Participants’ anxiety was assessed before, thirty minutes after, and three hours after the intervention via Spielberger State-Trait Anxiety Inventory. Results:The mean scores of state, trait, and total anxiety in the saffron group reduced significantly (p<0.05), while the mean scores in the other groups did not change significantly, except for the mean score of trait anxiety in the saffron-lippia group which decreased significantly (p=0.05). Therefore, after the intervention, the mean scores of state, trait, and total anxiety in the saffron group were significantly lower than the other groups (all, p<0.05). Conclusion:This study suggests that the oral use of a single-dose of 40 mg saffron extract is effective in alleviating anxiety among the candidates for CA.

Formulation and evaluation of capsules containing extracts of Cassia sieberiana for improved therapeutic outcome

In Ghana, the encapsulated blend of the powdered stem and root bark of Cassia sieberiana is prescribed and dispensed to patients at the Centre for Plant Medicine Research (CPMR), for the management of dysmenorrhea and gastric ulcer pain. This current formulation has significant challenges in manufacturing and optimization of therapeutic outcomes due to lack of standardization of actual quantities of the extracts obtained from ingestion of the product. The study sought to formulate and evaluate capsules of Cassia sieberiana using the stem and root bark. Extraction was undertaken with different solvents: absolute ethanol (F1) and 70% ethanol (F2). These 2 formulations were compared to the existing product (MP1) by CPMR. Granules for encapsulation were prepared by wet granulation and their flow properties compared with MP1. Drug-excipient compatibility was studied using FT-IR, TLC and UV. Quality control tests on MP1, F1 and F2 capsules were conducted using pharmacopoieal methods. From the results obtained, organoleptic and physicochemical properties of the extracts demonstrated its suitability for use in oral capsule formulation. MP1, F1 and F2 recorded a λmax of 278 nm, 278 nm and 276 nm, respectively. The extract per dose of capsules was found to be 27.84 ± 0.11 mg and 36.65 ± 0.03 mg for F1 and F2, respectively. Granules of F1 and F2 had good flow properties whereas MP1 demonstrated a fair flow property. FT-IR spectra showed possible interaction between extracts and excipients. However, TLC results indicated similar compounds present in the extracts and granules. The UV marker analysis also indicated no interaction since the percentage drug contents in F1 and F2 capsules were found to be 98.0% ± 1.40 and 98.90% ± 2.80 respectively. All 3 formulations passed the disintegration and uniformity of weight tests except MP1 which failed the latter. F1 capsules recorded the highest dissolution efficiency (99%) while MP1 recorded the lowest (22%). There was significant difference (p < 0.0001) in the release of Cassia sieberiana among the three formulations. This study has demonstrated the potential replacement of Cassia sieberiana capsules on the market with capsules developed from its extract with F1 capsules being the most desirable.

Postmastectomy Radiotherapy Using 5040 cGy in 28 Fractions for Patients with Immediate Breast Reconstruction: Institutional Outcomes

For patients planned to undergo adjuvant postmastectomy radiotherapy (PMRT) for breast cancer, immediate breast reconstruction (IBR) has been considered a relative contraindication. Delayed wound healing, increased risk of capsular contracture, fat necrosis, poor cosmesis, and rates of reoperation are of concern. Patients who have undergone IBR at our institution with an indication for PMRT are prescribed extended fractionation as per institutional policy. The aim of this quality assurance project is to review rates of reoperation for patients who received PMRT after IBR with autologous tissue (AT), tissue expanders (TE), or permanent implants (PI). Using a patient information system, patients were identified who underwent adjuvant PMRT to the chest wall and regional nodes to a total dose of 5040 cGy in 28 fractions between January 1, 2013 and January 31, 2019. Radiotherapy plans were reviewed. Medical records were reviewed for patient and treatment characteristics, and unexpected reoperation rate. Seventy-three patients underwent IBR and PMRT. Eleven (15.1%) patients had AT, 24 (32.9%) had TE, and 38 (52.1%) had PI. Twenty-four patients (32.9%) had documented cosmetic complications (including capsular contracture and asymmetry) after PMRT requiring reoperation. Cosmetic complications (CC) leading to reoperation were documented in 45.5% of patients with AT, 37.5% of patients with TE, and 26.3% of patients with PI. The mean elapsed time from PMRT completion to reoperation for cosmetic complications was 12.3 months (range = 2.3-33.1 months). Most patients received either adjuvant or neoadjuvant chemotherapy (97.3%). Of the patients having CC leading to reoperation compared to those without complication, a higher proportion received neoadjuvant chemotherapy, but this difference was not statistically significant (39.1% vs 19.4%, p = 0.135). For patients with CC leading to reoperation, there was a significantly higher volume of chest wall receiving ≥5040 cGy (851cc vs 680 cc, p = 0.023). Bolus was slightly more common in patients with CC but this difference was not statistically significant (91.7% vs 81.5, p = 0.461). For our cohort of patients receiving PMRT after IBR, the rate of CC is comparable to those quoted elsewhere. Interestingly, for our cohort, patients having PI had the lowest rate of CC leading to reoperation compared those with AT and TE. Patients with CC had a higher volume of chest wall receiving ≥ 5040 cGy. Further dosimetric analysis is needed to determine if there is a correlation with capsule dose and cosmetic outcomes.

The Presence of Lunasin, a Soy-Derived Bioactive Peptide in Plasma: A Randomized Clinical Trial

Abstract Objectives Lunasin is a bioactive peptide originally derived from soy protein which is being marketed as a nutraceutical product for its potential beneficial effects. Functionality of lunasin depends on its presence in circulation after digestion and metabolism. We studied safety, tolerability, and presence of lunasin in blood for the first time in humans in a well-controlled randomized clinical trial. Methods In a triple-blinded, placebo-controlled crossover study, 31 subjects (female: 19, male: 12, age = 61 ± 9.9 years) were randomized into an 8-week intervention period with capsules containing either 335 mg/d lunasin-enriched soy extract (LES) or corn fiber (placebo). This was followed by a 3-week wash-out period after which participants switched treatment groups for the next 8 weeks. In this crossover randomized study, plasma samples of subjects were collected after ingestion of a daily dose of lunasin-enriched capsules for 8 weeks, which provided 50 mg/d of lunasin. Enzyme-Linked Immunosorbent Assay was used to detect plasma lunasin level after an overnight fast. In order to assess the dietary intake of lunasin, two 24-hour dietary recalls (one in each intervention period) were obtained from each participant. Dietary intake data were collected and analyzed using Nutrition Data System for Research software version 2015, developed by the Nutrition Coordinating Center (NCC), University of Minnesota, Minneapolis, MN. Results During the intervention, no major safety concerns related to lunasin consumption were noticed. Ingestion of 335 mg/d LES for 8 weeks resulted in higher lunasin level in plasma compared to placebo. Fasting plasma lunasin levels ranged 0–10 ng/mL. The mean lunasin concentration in plasma increased by 44% after 8 weeks of daily supplementation with LES. Conclusions Lunasin was detectable in plasma after overnight fast in higher levels among LES takers. The difference in lunasin concentration was due to LES capsules and not dietary intake of lunasin-containing foods. Funding Sources The study was funded by Soy Labs Inc.

Pharmacokinetics and safety of olaparib in patients with advanced solid tumours and mild or moderate hepatic impairment.

Olaparib, a potent oral poly(ADP-ribose) polymerase inhibitor, is partially hepatically cleared. We investigated the pharmacokinetics (PK) and safety of olaparib in patients with mild or moderate hepatic impairment to provide dosing recommendations. This Phase I open-label study assessed the PK, safety and tolerability of single doses of olaparib 300-mg tablets in patients with advanced solid tumours. Patients had normal hepatic function (NHF), or mild (MiHI; Child-Pugh class A) or moderate (MoHI; Child-Pugh class B) hepatic impairment. Blood was collected for PK assessments for 96 hours. Patients could continue taking olaparib 300 mg twice daily for long-term safety assessment. Thirty-one patients received ≥1 dose of olaparib and 30 were included in the PK assessment. Patients with MiHI had an area under the curve geometric least-squares mean (GLSmean) ratio of 1.15 (90% confidence interval 0.72, 1.83) and a GLSmean maximum plasma concentration ratio of 1.13 (0.82, 1.56) vs those with NHF. In patients with MoHI, GLSmean ratio for area under the curve was 1.08 (0.66, 1.74) and for maximum plasma concentration was 0.87 (0.63, 1.22) vs those with NHF. For patients with mild or moderate hepatic impairment, no new safety signals were detected. Patients with MiHI or MoHI had no clinically significant changes in exposure to olaparib compared with patients with NHF. The safety profile of olaparib did not differ from a clinically relevant extent between cohorts. No olaparib tablet or capsule dose reductions are required for patients with MiHI or MoHI.

OP39 Treatment of ulcerative colitis With AMT-101, a novel oral interleukin-10 immunomodulatory fusion biologic that traffics across the intestinal epithelium

Abstract Background While different chronic inflammatory diseases can be correlated with distinct pro-inflammatory cytokines, interleukin-10 (IL-10) represents a central anti-inflammatory cytokine capable of modulating many pro-inflammatory signals. Previous clinical efforts to capture the benefit of IL-10 in suppressing the pro-inflammatory state in inflammatory bowel disease (IBD) patients have been limited by dose-limiting systemic side effects. Methods We have designed a chimaera of human IL-10 genetically fused to a non-toxic and poorly immunogenic fragment of the cholix exotoxin, termed AMT-101, that demonstrated rapid receptor-mediated transcytosis in vitro and in vivo and could activate phospho-STAT3 in cells within the lamina propria following luminal administration (data not shown). Mice with oxazolone-induced colitis were dosed by oral gavage with AMT-101 daily for 12 days, at which time colon tissue and serum were examined for hallmarks of inflammation. Enteric-coated capsules were used to deliver either 1 or 5 mg of AMT-101 to the distal ileum of cynomolgus monkeys; serum was collected to examine PK and PD outcomes in this non-inflamed model. Results Histological changes of colonic tissue associated with oxazolone-induced colitis was blocked by the oral gavage of AMT-101. Increases in serum levels of pro-inflammatory cytokines IL-1b, IL-6, and IL-17A were blunted by AMT-101 treatment. Remarkably, endogenous IL-10 increased in this model in an attempt to correct inflammation, but this was also decreased by the delivery of AMT-101. Cynomolgus monkeys dosed orally with AMT-101 capsules showed very low serum levels compared with those observed after IV injection of 0.5 mg/kg AMT-101. Strikingly, serum levels of IL-1 receptor antagonist (IL-1RA) as an anti-inflammatory PD marker were increased to a greater extent following oral capsule dosing compared with IV administration. Conclusion These studies provide strong pre-clinical evidence that AMT-101 can effectively reach the intestinal lamina propria to delivery biologically-active IL-10 following transcytosis across the intestinal epithelium. Importantly, the gut-selective nature of the responses observed suggests AMT-101 may alleviate the previous issues of dose-limiting side effects observed with systemic administration of IL-10 and point to the intestinal lamina propria as a critical site of IL-10’s immunomodulatory actions. AMT-101 has advanced to the clinic and is currently being evaluated in a Phase1b trial in patients with active ulcerative colitis.

Pharmacokinetics of piperine after oral administration of Sahastara remedy capsules in healthy volunteers.

Background and purpose:To investigate the pharmacokinetics of piperine after single oral doses of capsules containing Sahastara (SHT) remedy dried ethanolic extracts in healthy Thai volunteers.Experimental approach:Twenty-four healthy volunteers were divided into two dosage groups. They received a single oral dose of SHT remedy extract capsules of 100 or 200 mg. Blood was collected at time intervals of 0, 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 h. Acute clinical safety was monitored by complete physical examination and laboratory tests during the study period. Piperine concentration in blood and urine was determined by liquid chromatography tandem-mass spectrometry.Findings/Results:No serious adverse events were detected, only one volunteer had abdominal pain that was self-limiting. The pharmacokinetics of piperine following SHT remedy extract capsule administration demonstrated a mean peak concentration (Cmax) of piperine of 3.77 μg/mL and 6.59 μg/mL after dosing with 100 and 200 mg, respectively. Interestingly, a secondary maximum concentration of piperine was observed in this study, which might be related to enterohepatic recirculation. Negligible amounts of unchanged piperine were detected in urine.Conclusion and implication:The systemic exposure of piperine after SHT remedy ethanolic extract demonstrated dose proportionality after single oral dosing of 100-200 mg. Piperine was detectable in plasma for at least 48 h with evidence of enterohepatic recirculation. Metabolism and excretion profiles of piperine after administration of SHT remedy extract capsule need to be further explored for phytopharmaceutical product development.