Administration Of Oral Doses Research Articles

Gold-based nanospheres and nanorods particles used as theranostic agents: An in vitro and in vivo toxicology studies

The adverse effect of gold-based nanoparticles is still an open question since it depends on several factors as shape, surface charge or route of administration. In this study, we investigated the influence of shape and human serum albumin (HSA) coating on the adverse effects of spherical (AuNP) and nanorods (AuNR) gold-based particles. F C3H (fibroblast) and HTC (hepatocellular carcinoma) cell lines both from liver were exposed to 25, 75 and 125 μg mL−1, which correspond to 109 NP mL−1. For in vivo studies, Wistar rats received these materials by oral administration in doses of 10 μg kg−1 or 40 μg kg−1. Systemic toxicity was verified after 24 h and 48 h by morphological analysis, blood parameters and myeloperoxidase enzyme activity. Our results revealed that HSA corona does not influence totally the pathway of interactions between AuNP and AuNR. In vitro results evidenced that AuNP can decrease in at least 50% viability of F C3H and cell adhesion of HTC, but corona significantly overcomes these effects. No differences between shape or corona were observed in function of cell lines. In vivo studies showed that 40 μg kg−1 of AuNP-HSA caused an enhancement of the myeloperoxidase response indicating inflammatory processes. An increase from 40% to 80% on alkaline phosphatase levels were found for all groups. Our findings suggested that gold-based particles coated or not with HSA do not cause expressive adverse effects on in vitro or in vivo systems, and their oral administration cannot cause a systemic effect in the experimental conditions used here.

Population Pharmacokinetic/Pharmacodynamic Analysis of Nociceptive Pain Models Following an Oral Pregabalin Dose Administration to Healthy Subjects.

A battery of pain models can be used in clinical trials to investigate the efficacy and to establish the concentration‐effect relationship of novel analgesics. This study quantified the pharmacokinetics (PK) of pregabalin after a single oral dose of 300 mg and the pharmacodynamics (PD) on the pain tolerance threshold (PTT) of the cold pressor, electrical stimulation, the pressure pain model, and on the pain detection threshold of a contact heat pain model. The PK were best described using a one‐compartment model with lag time, linear absorption, and linear elimination. The PTT of the cold pressor showed a negative linear decrease over time without pregabalin. A linear drug effect was identified on the PTT of the cold pressor test and an on/off effect for the electrical stimulation PTT. No PK/PD relationship could be identified on the pressure pain and heat pain test. Citation:

A Population-Based Pharmacokinetic Model Approach to Pantoprazole Dosing for Obese Children and Adolescents.

Pharmacokinetic data for proton pump inhibitors (PPIs), acid-suppression drugs commonly prescribed to children, are lacking for obese children who are at greatest risk for acid-related disease. In a recent multi-center investigation, we demonstrated decreased, total body weight adjusted, apparent clearance (CL/F) of the PPI pantoprazole for obese children compared with their non-obese peers. Subsequently, we developed a population-based pharmacokinetic (PopPK) model to characterize pantoprazole disposition and evaluated appropriate pantoprazole dosing strategies for obese pediatric patients, using simulation. Pharmacokinetic data from the only prospective study of PPIs in obese children (aged 6-17years; n = 40) included 273 pantoprazole and 256 pantoprazole-sulfone plasma concentrations, after single oral-dose administration, and were used for pantoprazole model development and covariate analysis (NONMEM®). Model evaluation was performed via bootstrapping and predictive checks, and the final model was applied to simulate systemic pantoprazole exposures for common dosing scenarios. A two-compartment PopPK model, which included CYP2C19 genotype and total body weight, provided the best fit. Resultant, typical, weight-normalized pantoprazole parameter estimates were different than previously reported for children or adults, with significantly reduced pantoprazole CL/F for obese children. Of the dosing scenarios evaluated, the weight-tiered approach, approved by the US Food and Drug Administration, achieved pantoprazole exposures [area under the curve (AUC0-∞)] within ranges previously reported as therapeutic, without over- or under-prediction for obese children. Our data argue against empiric dose escalation of PPIs for obese children and support current FDA-approved pediatric weight-tiered dosing for pantoprazole; however, 3- to 5-fold inter-individual variability in pantoprazole AUC0-∞ remained using this dosing approach.

Effects of food and gender on pharmacokinetics of ticagrelor and its main active metabolite AR-C124910XX in healthy Chinese subjects .

The manuscript was mainly aimed to evaluate effects of food and gender on the pharmacokinetics of ticagrelor and its main active metabolite AR-C124910XX in healthy Chinese subjects observed in the bioequivalence studies of the two formulations of ticagrelor tablets. The single-dose, two-sequence, two-period and crossover studies were respectively conducted under fasting and fed conditions. Plasma samples were analyzed by an HPLC-MS/MS method. Log-transformed pharmacokinetic parameters of ticagrelor and AR-C124910XX obtained from the trials were compared by the mean of two one-sided t-test. Pharmacokinetic parameters of the two formulations were evaluated. The mean ticagrelor tmax value was delayed by 0.28-0.53 hours owing to meals. A 21.6-24.0% (p < 0.05) increase in the mean ticagrelor AUC* (body weight-normalized AUC) value was measured (fed vs. fasting). For AR-C124910XX, the mean T1/2 value was delayed by 0.84-1.33 hours (p < 0.05) due to meals. A 52.0-55.8% (p < 0.05) decrease in the mean Cmax* (body weight-normalized Cmax) value and a 15.6-16.9% (p < 0.05) decrease in the mean AUC* value were observed (fed vs. fasting). The female subjects exhibited higher exposures to ticagrelor and AR-C124910XX than the male subjects. Compared with other populations, the Chinese subjects in this study experienced a greater decrease in Cmax of AR-C124910XX due to meals. 21 adverse events of mild intensity occurred over the study periods. The studies showed food effects on the absorption of ticagrelor and the formation of AR-C124910XX, and gender effects on exposures to the drug after single oral-dose administration. .

What is an appropriate dose of voriconazole for the treatment of aspergillosis in African grey parrots (Psittacus erithacus)?

An African grey parrot ( Psittacus erithacus ) is presented to your practice with severe dyspnoea, inappetence and loss of body condition. Following a diagnostic workup, aspergillosis of the air...

Cocrystallization as a novel approach to enhance the transdermal administration of meloxicam

Despite its large effectiveness, the long-term oral administration of high doses of meloxicam (MLX) may lead to gastrointestinal events such as abdominal pain, diarrhea, dyspepsia, ulceration, hemorrhage, and gastrointestinal perforation. Moreover, the pH-dependent solubility of MLX makes the development of new oral formulations even more challenging. As an alternative to overcome these limitations, the transdermal delivery of this drug has been purposed. Although various physical and chemical approaches to enhance the absorption of MLX may be found in literature, the use of cocrystallization has not been reported so far. Cutaneous permeation of MLX and 1:1 meloxicam-salicylic acid cocrystal (MLX-SLC) were evaluated using Franz diffusion cells. Cocrystal was suspended in an aqueous solution and in a gel to evaluate the vehicle effect on permeation parameters. In aqueous medium, the cocrystallization showed to enhance the drug permeation coefficient from 1.38 to 2.15 × 10−3 cm/h. MLX-SLC generated supersaturation with respect to the drug during dissolution studies simulating the conditions in the Franz cell donor chamber. This greater amount of free drug in the solution could contribute to explain the higher transdermal absorption and shorter lag time of this system. In addition, the acidic coformer ionization led to a pH reduction from 7.4 to 5.8, which, in turn, provided an increase in the unionized species of the drug, enhancing its permeation rate. The gel containing cocrystals reduced MLX permeation rate significantly (P = 0.42 × 10−3 cm/h), which was attributed to its higher viscosity.

Phytochemical Screening, Acute Toxicity , Analgesic And Anti-Inflammatory Effects Of Apricot Seeds Ethanolic Extracts

The aim of present study was to investigate the phytochemical screening, acute toxicity and some pharmacological activities of ethanolic extract 70 % and 99.9% of apricot seeds. The phytochemical screening was done for determination of total phenolic compounds by Folin–Ciocalteu method, total flavonoids by aluminum chloride colorimetric method and total carotenoids by colorimetric method. The acute toxicity was done for determination of LD50 in mice by oral administration of upgraded doses of the extracts. The anti-inflammatory activity was done in vivo by formalin-induced paw edema in rats. The analgesic activity was carried out in mice by writhing test and hot plate method. Phytochemical screening revealed that the amount of total phenolic compounds was 179.4 and 191.2 µg gallic acid equivalent / g dry extract and the amount of total flavonoids was 226.18 and 509.34 µg rutin equivalent / g dry extract and the amount of total carotenoids was 0.145 and 0.156 mg/g dry extract for 70 % and 99.9% ethanolic extract, respectively. The acute toxicity revealed that both extracts had no toxic symptoms in rats and no mortalities appear by upgraded doses of 1 g to 10 g / kg b.wt. The 70% and 99.9% ethanolic extracts exhibited significant analgesic and anti-inflammatory activites in a dose of 100 mg/kg b.wt. of both extracts. These results suggest that apricot seed extracts contain significant level of safe non-toxic phytochemical substances that have significant analgesic and anti-inflammatory activities.

Pharmacokinetics of Riluzole in Beagle Dogs.

Riluzole is a benzothiazole anticonvulsant used in the treatment of patients with amyotrophic lateral sclerosis and it is being investigated for clinical use in patients with spinal cord injury. The present study evaluated the pharmacokinetics of riluzole in beagle dogs after oral dose administration. The oral doses (1.5, 5, 15 and 50 mg/kg) of riluzole were administered to beagle dogs and blood samples were collected from 0 h to 24 h post drug administration. Riluzole was quantified by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The method was sensitive, precise, accurate and selective to riluzole quantification in plasma of beagle dogs. The pharmacokinetics following oral administration was linear from 1.5 to 15 mg/kg and the t1/2 was 2.16, 1.5, 1.8 and 3.0 h after oral administration of 1.5, 5.0, 15 and 50 mg/kg riluzole. The riluzole pharmacokinetics was linear up to 15 mg/kg and had a significantlyshorter t1/2 in beagle dogs than in humans.

BIOANALYTICAL METHOD DEVELOPMENT OF ATENOLOL IN RAT PLASMA BY ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY AND TANDEM MASS SPECTROMETRY METHOD: APPLICATION TO PHARMACOKINETIC DRUG-HERB INTERACTION STUDY

Objective: To develop a rapid, simple and sensitive ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS) method for quantitative estimation of atenolol (ATN) in rat plasma and its application to pharmacokinetic drug-herb interaction study.Methods: Simple precipitation method was used for the extraction of plasma samples with an aliquot of 25 μl plasma samples extracted using acetonitrile precipitation technique containing internal standard. Chromatographic separation was performed using Phenomenex, Kinetex, C18, 50 x 2.1 mm, 1.7µ by a gradient mixture of 0.1 % formic acid in acetonitrile and 10 mmol Ammonium formate as a mobile phase at the flow rate of 0.7 ml/min. The analyte was protonated in the positive electrospray ionization (ESI) interface and detected in multiple reactions monitoring (MRM) modes using the transition m/z 145.0-267.2.Results: The developed method had an advantage of fast chromatography run time of 1.8 min with improved sensitivity over existing methods and broader application to use for drug-herb or drug-drug interaction studies in rat pharmacokinetic. Calibration curves have been linear over the wide range of 4.93-5047.00 ng/ml in rat plasma which covers a wide range of plasma concentrations form study samples. ATN is widely used as a biomarker for determination of the drug-herb or drug-drug interactions studies, especially with the drugs that alter the permeability of another administered drug(s) and the developed method can be used to explore drug interaction studies. Especially to evaluate the role of concurrently administered drugs and its impact on permeability enhancer or absorption enhancer drugs following oral dose administration. This method will be significantly useful for the drug-herb pharmacokinetic interaction studies where we cannot quantify the herb because of multiple components in the hydro-alcoholic or aqueous extract of any herb, so choice remained is to quantify ATN and therefore it will be extremely helpful in such scenario.Conclusion: It was concluded that the developed UPLC-MS/MS method was sensitive linear and rapid; can be used for quantification of ATN in rat plasma for pharmacokinetic drug-herb interaction study.

Abstract 4792: Preclinical evaluation of GST-HG161, a potent and highly selective c-MET inhibitor

Abstract Objective: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Studies indicate that aberrant activation of mesenchymal-epithelial transition factor (c-MET) is associated with HCC development. Blocking c-MET signaling shows antitumor efficacy in patients with HCC. Thus, c-MET has been an attractive therapeutic target for HCC. We disclose here for the first time a potent and selective c-MET inhibitor GST-HG161 and show the antitumor efficacy data in preclinical models of HCC. Method: MHCC97H HCC cell line with c-MET overexpression was used to evaluate the anti-proliferative activity of GST-HG161 in a 120-hour viability assay. Selectivity was evaluated with a panel of cell lines without overexpression of c-MET. Daily oral administration of GST-HG161 doses of 1, 3, 10 and 30mg/kg was used to evaluate its in vivo antitumor efficacy in two animal models of HCC with c-MET overexpression, MHCC97H xenograft (CDX) model and LI-03-0317 xenograft (PDX) model. The c-MET protein levels and gene copy number in LI-03-0317 PDX were assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. High c-MET expression in LI-03-0317 PDX was determined by the presence of tumor cells with membrane staining of 3+ intensity. Effect of GST-HG161 on c-MET signaling inhibition was assessed by western blot analysis of downstream effector proteins including p-MET, p-AKT and p-ERK. Result: GST-HG161 displayed potent anti-proliferative activity in MHCC97H HCC cell line (IC50 = 5 nM) while showed little activity in the cell lines without c-MET overexpression. It significantly inhibited tumor growth at tested doses (3, 10 and 30mg/kg) (P&amp;lt;0.05) in both MHCC97H CDX model and LI-03-0317 PDX model. In MHCC97H CDX model, western blot analysis showed that GST-HG161 potently inhibited p-MET and downstream effector proteins p-AKT and p-ERK in the tumor tissue, indicating that the tumor growth inhibition in this model was mediated through inhibition of c-MET. Conclusion: GST-HG161 is a potent and highly selective c-MET inhibitor. Its excellent antitumor efficacy as shown in the HCC mouse models provide us with confidence that GST-HG161 has high potential in the clinic for treating patients of HCC with high c-MET activity. Citation Format: Xiongbin Xu, Gang Li, Lihong Hu, Junguo Hao, Charles Z. Ding, Shuhui Chen. Preclinical evaluation of GST-HG161, a potent and highly selective c-MET inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4792.

Effects of Durian Fruit on Blood Pressure of Spontaneously Hypertensive Rats

Durian or scientifically known as Durio zibethinus is one of the most well-known seasonal fruits in the Southeast Asia region. However, its safe consumption in individuals with hypertension is still controversial. This study was conducted to investigate the effect of durian on blood pressure of spontaneously hypertensive rat model. Four groups of rats (n=5) were fed with either a low dose durian (26 g/kg), a high dose durian (52 g/kg), sugar solution (8 mL/kg) which has similar sugar composition in the durian as placebo control, and distilled water as vehicle control (8 mL/kg) for 14 days. The durian doses for rats were obtained by converting from human doses. Baseline reading of blood pressure and heart rate were recorded before the first oral administration of durian. The blood pressure and heart rate were also measured 1 h after the durian oral administration on day 1, 3, 7 and 14 of the experiment. In conclusion, durian fruit possessed an acute effect on the blood pressure of hypertensive rats but heart rate was unaffected. High dose administration of durian led to significant elevation of blood pressure after 1 h of consumption. Meanwhile, low dose of durian (26 g/kg) caused an insignificant reduction in systolic and diastolic blood pressure. Tolerance to the durian fruit was observed after three to seven days of the oral administration and low dose consumption of durian fruit was safe in the hypertensive rat.

Alteration of UDP-glucuronosyltransferase 1a1, 1a7 and P-glycoprotein expression in hepatic fibrosis rats and the impact on pharmacokinetics of puerarin

BackgroundPuerarin, derived from a traditional Chinese herb Pueraria lobata (Willd.) Ohwi which was distributed globally and planted in most parts of China, has been extensively applied in patients with cardiovascular diseases in China. Yet a considerable proportion of the patients were accompanied with liver illnesses simultaneously because of all sorts of reasons. Hypothesis/PurposeIt had been implied by some previous research that the absorption and the metabolism of puerarin were susceptible to liver issues due to changed P-gp and Ugt1a level, but pharmacokinetics of puerarin under such conditions were few concerned. Our study aimed to make sure whether and how much the behavior of puerarin in vivo was affected by hepatic diseases, and to explore the potential mechanisms. MethodsA CCl4 induced rat model of hepatic fibrosis (HF) was prepared and verified. Single low/high doses of oral and intravenous administration of puerarin to HF and normal rats were performed. Pharmacokinetics of puerarin were determined by a validated HPLC method. The expression of P-gp, Ugt1a1, and Ugt1a7 in both liver and intestines were determined by quantitative RT-PCR and Western blot analysis respectively. ResultsThe systemic exposure of puerarin in HF rats of experimental groups were found decreased remarkably except for that of the high dose intravenous group. Moreover, the expression of P-gp, Ugt1a1, and Ugt1a7 in liver and intestines of HF rats were figured out increased. ConclusionThe results indicated that the HF originated overexpression of Ugt1a1, Ugt1a7, and P-gp level played important roles in pharmacokinetics of puerarin, suggested the clinical regimen of puerarin based on normal populations might be inappropriate for patients with chronic liver diseases. It was implied drugs whose absorption or elimination were related to P-gp, Ugt1a1, or Ugt1a7 might also be affected by hepatic illnesses.

Antidiabetic Effect of JP-2266, a Novel SGLT1/2 Dual Inhibitor, for the Treatment of Type 1 Diabetes

JP-2266, a potent, a new synthetic small molecule, is highly selective sodium glucose cotransporter (SGLT) 1 and 2 inhibitor, and offers new therapeutic regimen by improving glycemic control for type 1 diabetes mellitus (T1DM). Insulin used for blood glucose lowering, which is an important agent in controlling blood glucose in T1DM patients, however, it is not easy to be administrated due to inconvenience of injection and hypoglycemic risk. JP-2266, as adjunct therapy to insulin, is expected to overcome the shortcomings of insulin monotherapy in T1DM. We discovered JP-2266, a preclinical candidate to develop as an agent for the treatment of type 1 diabetes. IC50 values of JP-2266 were 10.1 nM and 1.3 nM, respectively, for SGLT1 and SGLT2 in vitro glucose uptake assay. Sotagliflozin which is known as a SGLT1 and 2 dual inhibitor was 36 nM and 1.8 nM, respectively, in vitro glucose uptake assay. Also JP-2266 showed a significant decrease postprandial blood glucose level in type 1 diabetes rat models. When JP-2266 was treated with 1, 2, or 5 mg/kg by single oral administration in streptozotocin (STZ)-induced T1DM rat model, AUC0-4h (mg·h/dL) for 4 hours in OGTT was 38.4%, 48.1% and 56.4%, respectively, compared to vehicle treated group. Moreover, STZ rats treated with 5mg/kg of JP-2266 showed the same AUC0-4h reduction rate as the high-dose insulin treated group (1.8U/kg), and blood glucose reduction rate of JP-2266 and Sotagliflozin at 10 mg/kg was 49.4% and 39.1%, respectively, compared to vehicle treated group in oral repeated administration for 28 days. Additionally, HbA1c of JP-2266 treated group was 6.4%, while Sotagliflozin treated group was 7.2% at 10 mg/kg. We suggest that JP-2266 will be a potent candidate agent for the treatment of T1DM, since JP-2266 has a more potent reducing effect on hyperglycemia in OGTT and showed comparable effect by oral repeated dose administration than those of Sotagliflozin. Disclosure Y. Park: None.

Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes.

Ibogaine may be effective for transitioning opioid and cocaine dependent individuals to sobriety. American and European self-help groups provided public testimonials that ibogaine alleviated drug craving and opioid withdrawal symptoms after only a single dose administration. Preclinical studies in animal models of addiction have provided proof-of-concept evidence in support of these claims. However, the purported therapeutic benefits of ibogaine are based on anecdotal reports from a small series of case reports that used retrospective recruitment procedures. We reviewed clinical results from an open label case series (N = 191) of human volunteers seeking to detoxify from opioids or cocaine with medical monitoring during inpatient treatment. Whole blood was assayed to obtain pharmacokinetic measures to determine the metabolism and clearance of ibogaine. Clinical safety data and adverse events (AEs) were studied in male and female subjects. There were no significant adverse events following administration of ibogaine in a dose range that was shown to be effective for blocking opioid withdrawal symptoms in this study. We used multi-dimensional craving questionnaires during inpatient detoxification to test if ibogaine was effective in diminishing heroin and cocaine cravings. Participants also completed standardized questionnaires about their health and mood before and after ibogaine treatment, and at program discharge. One-month follow-up data were reviewed where available to determine if ibogaine’s effects on drug craving would persist outside of an inpatient setting. We report here that ibogaine therapy administered in a safe dose range diminishes opioid withdrawal symptoms and reduces drug cravings. Pharmacological treatments for opioid dependence include detoxification, narcotic antagonists and long-term opioid maintenance therapy. Our results support product development of single oral dose administration of ibogaine for the treatment of opioid withdrawal during medically supervised detoxification to transition drug dependent individuals to abstinence.

Bidirectional Pharmacokinetic Interaction Between Amodiaquine and Pioglitazone in Healthy Subjects.

Amodiaquine (AQ) and pioglitazone (PGZ) are both metabolized by CYP2C8, an enzyme also inhibited by PGZ. These drugs are likely to be administered in instances of comorbidity of malaria with type 2 diabetes. This study, hence, evaluated the possibility of a drug interaction resulting from the concurrent use of both drugs. A 3-period crossover design in 10 healthy subjects, that assessed the disposition of AQ and PGZ alone and when coadministered, was implemented with the administration of single oral doses of AQ and PGZ. Whole-blood samples collected between 0 and 24hours on protein saver cards across the study periods were processed and analyzed for AQ and PGZ contents. Pharmacokinetic parameters were derived by a noncompartmental analysis. Geometric mean ratios for the Cmax , area under the concentration-time curve for 24 hours (AUC0-24h ), and AUC0-∞ , alongside their corresponding 90%CIs, were compared across the study periods to infer clinically significant changes in disposition. The coadministration of AQ and PGZ resulted in decreases of about 38% and 54% in the Cmax and AUC0-24h of AQ, respectively. For PGZ, the Cmax increased by about 50%, and AUC0-24 rose by 48%. The 90%CIs of geometric mean ratios for the Cmax , AUC0-24h , and AUC0-∞ were all outside the expected bioequivalence interval of 80% to 125% for both drugs, implying significant interactions. These findings suggest that a bidirectional interaction between AQ and PGZ, with likely implications for the therapy and toxicity of both drugs, may occur in the event of their coadministration.

Determination and pharmacokinetic study of guaiol in rat plasma by gas chromatography–mass spectrometry with selected ion monitoring

Guaiol has been used for thousands of years as a traditional Uygur medicine and is the primary active component found in Ferula ferulaeoides (Steud.) Korov (F. ferulaeoides). In our present study, a rapid, selective, and sensitive method of monitoring selected ions was established based on gas chromatography-mass spectrometry. This method was optimized for the quantification and pharmacokinetic analysis of guaiol in rat plasma following oral administration of chloroform extract from Ferula ferulaeoides. Plasma was extracted using liquid-liquid extraction with ethyl acetate and was analyzed on a HP-5MS column (30 m × 250 μm × 0.25 μm) with a mass selective detector. Detection was carried out under selected ion monitoring mode, and three selected ion monitoring ions (m/z 59.1, 107.1, and 161.1 for guaiol) were used for the quantitative determination of that under investigation. The assay demonstrated excellent linearity in the range of 1–200 ng/mL (r = 0.9993, n = 8) in the case of guaiol measured in rat plasma. The limit of detection and the limit of quantification for guaiol in rat plasma were found to be 0.25 ng/mL and 1 ng/mL, respectively. Intra-day and inter-day precisions were expressed as the relative standard deviation for the method and were in the range of 97.49%–106.16% and 97.04%–105.91%, respectively. Extraction efficiencies were all determined to be >90%, and recoveries were ranged from 91.25% to 96.24%. This method has been successfully applied for the pharmacokinetic evaluation of chloroform extract isolated from F. ferulaeoides following a single oral administration dose (157.5 mg/kg) in rats. The guaiol pharmacokinetic study demonstrated that the half-life of guaiol was 9.18 ± 3.75 h, the mean residence time was 9.07 ± 3.86 h, the maximum guaiol concentration in the plasma was 28.63 ± 6.82 ng/mL, and the maximum time guaiol was in the plasma was 0.50 h.

Absorption, metabolism, and excretion of [14C]evogliptin tartrate in male rats and dogs

ABSTRACTThe objective of this study was to determine the absorption, excretion, and metabolism of a novel, oral antihyperglycemic drug, evogliptin, in male rats and dogs. Plasma, urine, feces, and expired air samples were collected after a single oral dose administration of [14C]evogliptin, samples were analyzed by measuring overall radioactivity levels using high-performance liquid chromatography (HPLC), and radioactivity levels were measured by utilizing LC-tandem mass spectrometry (LC-MS/MS). The total amounts of radioactivity excreted in urine, feces, and expired air up to 168 h after administration of [14C]evogliptin tartrate to rats (30 mg evogliptin/kg) and dogs (10 mg evogliptin/kg) were 96.7% and 96.8% of initial doses administered, respectively. The extent of urinary and fecal excretion in the rat up to 168 h constituted 29.7% and 66.5% of the given dose, respectively; and in dog was 43.3% and 53.5%, respectively. A total of 23 possible metabolites were detected with radiochromatograms of plasma, urinary, and fecal samples, but only the structures of 12 metabolites were identified via LC-MS/MS analysis. Evogliptin was the major component. Regarding the total radiochromatographic peak areas, peaks 9 (evogliptin acid) and 11 (hydroxyevogliptin) were the major metabolites in rats, and peaks 8 [4(S)-hydroxyevogliptin glucuronide], 15 [4(S)-hydroxyevogliptin], and 17 [4(R)-hydroxyevogliptin] were the predominant metabolites in dogs. Data demonstrated that evogliptin was the major component excreted in urine and feces of rats and dogs, but the metabolite profiles varied between species.

Preliminary toxicity and thin layer chromatographic studies of Pteleopsis habeensis leaves

Oral acute toxicity test in which a single dose is used in an animal on one occasion is to identify the gross behaviour and the dose that will cause the animal to die. To investigate the phytoconstituents and toxicity of different extracts of P. habeensis in wistar strain Albino rats. The acute toxicity was determined through oral administration of different doses of P. haeensis leaf extracts to Wistar albino rats in increasing concentrations to ascertain its safety. The animals were monitored daily for 10 days for signs of toxicity such changes in their general behaviour and death as endpoint. The lethal dose (LD50) of P. habeensis leaves extract were found to be ≥ 4000 mg/kgand there was no any sign of toxicity or changes in the gross behaviour when observed. The extracts were found to contain some important phytochemical constituent such as alkaloid, flavonoids, Tannin and Triterpenoids. TLC studies illustrated the spots of different phytoconstituent presents. The findings revealed that with the different extracts of P. habeensis no sign of toxicity on short term exposure of a single dose and contains different active constituent which are associated with some pharmacological effects.

Preliminary toxicity and thin layer chromatographic studies of Pteleopsis habeensis leaves

Oral acute toxicity test in which a single dose is used in an animal on one occasion is to identify the gross behaviour and the dose that will cause the animal to die. To investigate the phytoconstituents and toxicity of different extracts of P. habeensis in wistar strain Albino rats. The acute toxicity was determined through oral administration of different doses of P. haeensis leaf extracts to Wistar albino rats in increasing concentrations to ascertain its safety. The animals were monitored daily for 10 days for signs of toxicity such changes in their general behaviour and death as endpoint. The lethal dose (LD50) of P. habeensis leaves extract were found to be ≥ 4000 mg/kgand there was no any sign of toxicity or changes in the gross behaviour when observed. The extracts were found to contain some important phytochemical constituent such as alkaloid, flavonoids, Tannin and Triterpenoids. TLC studies illustrated the spots of different phytoconstituent presents. The findings revealed that with the different extracts of P. habeensis no sign of toxicity on short term exposure of a single dose and contains different active constituent which are associated with some pharmacological effects.

An in vitro - in silico approach for the formulation and characterization of ranitidine gastroretentive delivery systems

Contemporary trends in the pharmaceutical development emphasize the utility of advanced computer tools to facilitate formulation of new medicines. A special attention has been given to the formulation and characterization of dosage forms for targeted drug delivery that can improve therapeutic outcome. The objective of this study was to apply the combined in vitro-in silico approach to optimize the design of gastroretentive floating system for sustained release of ranitidine hydrochloride. Formulation of the floating systems was based on the effervescent effect of sodium-bicarbonate, whereas prolonged release of ranitidine hydrochloride was provided by the hydrophilic polyethylene oxide polymers which swell and form a gel layer on the surface of the floating tablets. Dosage form floating characteristics and drug dissolution were investigated under biorelevant conditions simulating stomach environment. The obtained dissolution data were used as inputs in ranitidine-specific physiologically-based pharmacokinetic model within GastroPlus™ software to predict the expected pharmacokinetic profiles following oral administration of the designed formulations. The predictive power of the designed model was tested by comparing the simulation outcomes with literature values on drug plasma concentration-time profiles following intravenous and oral administration of different ranitidine doses. In addition, simulation results demonstrated increased extent of drug absorption with prolonged gastric residence times.