Multiple-dose Group Research Articles

A comparative interventional study on the efficacy of single and multiple dose combination drug regimen of leucorrhea among women in reproductive age group

Background: Reproductive tract infections (RTIs) in women are becoming major public health problem not only in India but also over the world. Syndromic approach is advocated by World Health Organization (WHO) to manage common RTIs using clinical flow charts based on identifying a syndrome that cause the symptoms reported by patients. The most commonly reported among the women with RTIs is abnormal vaginal discharge or Leucorrhea. Single dose regimen is not preventing the recurrence of infections. A second course of treatment is required followed by standard single dose regimen for achieving better cure rate in chronic vaginal discharge. Objective of the study was to compare the efficacy of single dose drug combination regimen with multiple dose regimens in the treatment of leucorrhoea. Methods: Quasi-experimental study was done in Urban field service area, RMMCH – Chidambaram among Married women in the reproductive age group (15-49 years) with complaints of abnormal vaginal discharge for ≥15 days coupled with any one of the symptoms suggestive of RTI. The study subjects were categorized into two groups – one with single dose regimen and the other with multiple dose regimen. Follow up was done on day 7, 15 and after 6 months of therapy. Results: A total of 113 subjects were recruited with 57 participants in single dose group and 56 in multiple dose groups. The subjects who received single dose had a better cure rate as compared to multiple dose group on day 7(87.7% & 85.7%), day 15 (94.7% & 89.3%) and after six months (84.2% & 76.8%) assessment respectively. Recurrence rate was found to be equal in both the groups. Our study indicates that variables such as age of the study subjects and type of flow had significant association with the outcome. Conclusions: Single-dose therapy is as effective as multiple- dose in the management of vaginal discharge based solely on symptoms. The multiple drug regimens can be given if the symptoms persist after single drug regimen as the chances of developing complications due to chronic vaginal discharge are high.

A New Approach to PCSK9 Therapeutics.

PCSK9 inhibition is an effective therapy to reduce LDL cholesterol (LDL-C) and cardiovascular events. A recent study shows that one or two doses of inclisiran, a long-acting synthetic small-interfering RNA (siRNA) that selectively targets hepatic PCSK9, causes a sustained reduction of plasma LDL-C for up to 6 months. Pending further studies of safety and efficacy, this may represent an important addition to the armamentarium for inhibiting PCSK9.

Repeated doses of cardiac mesenchymal cells are therapeutically superior to a single dose in mice with old myocardial infarction.

We have recently demonstrated that repeated administrations of c-kitPOS cardiac progenitor cells (CPCs) have cumulative beneficial effects in rats with old myocardial infarction (MI), resulting in markedly greater improvement in left ventricular (LV) function compared with a single administration. To determine whether this paradigm applies to other species and cell types, mice with a 3-week-old MI received one or three doses of cardiac mesenchymal cells (CMCs), a novel cell type that we have recently described. CMCs or vehicle were infused percutaneously into the LV cavity, 14days apart. Compared with vehicle-treated mice, the single-dose group exhibited improved LV ejection fraction (EF) after the 1st infusion (consisting of CMCs) but not after the 2nd and 3rd (vehicle). In contrast, in the multiple-dose group, LV EF improved after each CMC infusion, so that at the end of the study, LV EF averaged 35.5±0.7% vs. 32.7±0.6% in the single-dose group (P<0.05). The multiple-dose group also exhibited less collagen in the non-infarcted region vs. the single-dose group. Engraftment and differentiation of CMCs were negligible in both groups, indicating paracrine effects. These results demonstrate that, in mice with ischemic cardiomyopathy, the beneficial effects of three doses of CMCs are significantly greater than those of one dose, supporting the concept that multiple treatments are necessary to properly evaluate the full therapeutic potential of cell therapy. Thus, the repeated-treatment paradigm is not limited to c-kit POS CPCs or to rats, but applies to other cell types and species. The generalizability of this concept dramatically augments its significance.

Repeated Administrations of Cardiac Progenitor Cells Are Markedly More Effective Than a Single Administration: A New Paradigm in Cell Therapy.

The effects of c-kit(POS) cardiac progenitor cells (CPCs, and adult cell therapy in general) on left ventricular (LV) function have been regarded as modest or inconsistent. To determine whether 3 CPC infusions have greater efficacy than 1 infusion. Rats with a 30-day-old myocardial infarction received 1 or 3 CPC infusions into the LV cavity, 35 days apart. Compared with vehicle-treated rats, the single-dose group exhibited improved LV function after the first infusion (consisting of CPCs) but not after the second and third (vehicle). In contrast, in the multiple-dose group, regional and global LV function improved by a similar degree after each CPC infusion, resulting in greater cumulative effects. For example, the total increase in LV ejection fraction was approximately triple in the multiple-dose group versus the single-dose group (P<0.01). The multiple-dose group also exhibited more viable tissue and less scar, less collagen in the risk and noninfarcted regions, and greater myocyte density in the risk region. This is the first demonstration that repeated CPC administrations are markedly more effective than a single administration. The concept that the full effects of CPCs require repeated doses has significant implications for both preclinical and clinical studies; it suggests that the benefits of cell therapy may be underestimated or even overlooked if they are measured after a single dose, and that repeated administrations are necessary to evaluate the effectiveness of a cell product properly. In addition, we describe a new method that enables studies of repeated cell administrations in rodents.

Single dose versus multiple dose prophylactic antibiotic in laparoscopic cholecystectomy: a comparative study

Background: Our study is aimed to compare the impact of single vs. multiple dose of antibiotic in laparoscopic cholecystectomy in terms of post-operative infection related complications. Methods: The present study was prospective and longitudinal. Protocol of the procedure was formed along with Performa, Patient Information Sheet and Informed Consent Form. This study was carried out from January 2013 to June 2015 in surgery department of a secondary care hospital of Gujarat state. Total 180 patients who were admitted for elective laparoscopic cholecystectomy were included in our study. The patients were randomly divided in two equal groups: single dose (SD) group and multiple dose (MD) group, comprising of 90 patients in each group. SD group was given ceftriaxone (2 gm) intravenously at the time of induction of anaesthesia. Whereas, MD group was given ceftriaxone (2 gm) intravenously at the time of induction of anaesthesia followed by ceftriaxone (1 gm) intravenously twice a day for two days post-operatively. Results: In single dose antibiotic group, total post-operative infection rate was 4.4% and that in multiple dose groups was found to be 3.3%. Data was analysed with Chi- square test and the difference in the rate of SSI in both the groups was found statistically insignificant. Conclusion: The rate of post-operative SSI after single dose antibiotic intravenously at induction of anaesthesia is comparable with that of multiple dose antibiotics. So single dose antibiotic regimen can be safely practiced in elective laparoscopic cholecystectomy.

Abstract 3242: Xenograft dose-response from intra-mouse dose escalation

Abstract Introduction Xenograft response has been shown to hold predictive value for the clinical efficacy of a drug, but growth sensitivity to a drug candidate can vary widely between xenografts models. As the ability to test pre-clinically for broad biological activity across many xenografts models is often resource-limited, in this work we develop a mathematical approach based on evolutionary dynamics to derive dose-response information from a single xenograft tumor. Methods We propose to estimate a dose-response curve of xenograft growth inhibition by treating a single tumor with a series of different dose strengths. Exponential tumor growth rate (GR) may be quickly estimated to determine the inhibition effect of a particular exposure during week-long intervals of constant dose strength. We next considered the possibility of a dose strength ordering effect on tumor growth due to cellular heterogeneity in GR and drug sensitivity within a tumor. To determine to what extent dose history could influence the observed growth inhibition, we developed an evolutionary model of tumor growth for a heterogeneous population of cancer cells with joint-distributed clonal GR and drug sensitivities, and simulated tumor response to treatment for distributions having variable degrees of correlation. Finally, we tested the ability to estimate dose-response curves from single tumors in vivo compared to the typical method of assessing drug effect based on multiple dose-groups. Results For the three possible orders of dosing three different treatment strengths, we found that the simulated study design with escalating dose intervals lead to the least error compared to assessing each dose in a separate tumor. Additionally, the discrepancy between the growth inhibition effects of different dose orders peaks when the correlation between GR and drug sensitivity decreases to negative. We then show that this study design allows efficient, accurate estimation of the range of dose-responses in a broad set of simulated tumor types (e.g., fast-growing and sensitive, or slow-growing and insensitive). An in vivo dose-response study validates the estimation of dose-response curves from a single xenograft by comparing favorably with the single dose per mouse method. Conclusions The mathematical approach described here allows efficient estimation of a dose-response curve for a xenograft model using a single tumor. By reducing the resources required to determine the response of a single model, a molecule's anticancer effect can be tested against a larger sample of tumor types pre-clinically. A more accurate picture of a drug candidate's broad biological activity will allow for greater confidence in translational projections of clinical efficacy. Citation Format: Andrew Chen, Christopher J. Zopf, Jing-Tao Wu, Wen Chyi Shyu, Arijit Chakravarty. Xenograft dose-response from intra-mouse dose escalation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3242. doi:10.1158/1538-7445.AM2015-3242

Abstract 4862: PredICT: a novel solution for capturing, assembling and combining in vivo data

Abstract Historically, within large pharmaceutical R&amp;D organisations, the inherent complexity and diversity of preclinical in vivo PKPD and efficacy data has encouraged a culture in which data capture and storage is generally informal and spreadsheet-based. This makes data sets both hard to find and hard to accurately interpret and limits the useful lifetime of the data. Cross-study analysis becomes inherently difficult, time-consuming and error-prone due to the manual effort required to identify, obtain, understand, collate and transform data sets from multiple studies into appropriate formats for visualisation and analysis. With ever more sophisticated studies being generated exploring doses, schedules and combinations, and with the increased reliance on quantitative systems pharmacology approaches to support drug projects, there is considerable need to treat data as the vital asset it is recognised to be, and to secure and exploit it in an effective way. PredICT is a novel platform built to integrate, manage and analyse in vivo data in a much more coherent fashion. The requirements in terms of the data workflow tools of in vivo pharmacologists and modelling scientists were determined which required the development of features that enable effective data organisation and flow. Specifically (1) data capture tools that integrate into the existing scientist workflow enabling efficient and automated data upload; (2) a generalised language and database for storing in vivo studies including the full details of the dosing regime and measured endpoints; (3) a data query tool and interface to quickly and efficiently identify the studies and data of interest in order to collate and present a summarised set of results; (4) an automated export feature to deliver data into formats that can be directly imported into visualisation and modelling software. Complex Oncology in vivo studies assessing multiple dose and schedule groups can be expressed in the database, providing all the primary and meta-data to re-create the experiment numerically. These studies can then be visualised in a query tool that collates data from across multiple studies to enable integrated analysis. PredICT platform has transformed the way in which all project scientists handle in vivo data at AstraZeneca. For in vivo pharmacology scientists the benefits are a more streamlined workflow for the capture and storage of data, along with an effective and efficient tool for identifying and retrieving data from across multiple studies, projects and in vivo models into a single data table. For modelling &amp; simulation scientists, it has reduced the proportion of time spent dealing with data organisation from approximately 50% to less than 5%, allowing them to focus on deriving scientific insight rather than hunting for and manually collating data sets. More broadly, the platform secures in vivo data in a consistent and robust manner, which ensures data integrity for long term use and reference. Citation Format: Rhys DO Jones, Marie Cooke, James Hinchliffe, Justin Morley, Simon T. Barry. PredICT: a novel solution for capturing, assembling and combining in vivo data. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4862. doi:10.1158/1538-7445.AM2015-4862

Evaluation of human skin tolerance to creams containing tazarotene and betamethasone dipropionate

Objective To evaluate skin tolerance to creams containing different concentrations of tazarotene and betamethasone dipropionate in healthy volunteers after single or multiple applications, and to predict potential adverse effects of these creams as well as their degree. Methods Thirty-four healthy volunteers were enrolled in a single-dose trial group, and divided into six subgroups to receive single session of topical treatment with creams containing tazarotene and betamethasone dipropionate both at the concentrations of 0.025%, 0.05%, 0.1%, 0.15%, 0.2% and 0.25% respectively. Another 12 healthy volunteers were enrolled in a multiple-dose trial group, and divided into two subgroups to topically apply creams containing tazarotene and betamethasone dipropionate both at the concentrations of 0.2% and 0.15% , respectively, once a day for 7 consecutive days. General status and subjective feelings of these testees were evaluated, skin reactions at application sites were observed, and routine laboratory examinations(including routine blood test, routine urine test, hepatic and renal function examination)were performed, before and after the application of these creams in both single-and multiple-dose trials. Endogenous cortisol levels were measured before and 7, 14 days after the initial application of the creams, and the amount of drugs percutaneously absorbed into systemic circulation was determined before and 1, 3, 5, 7 days after that in the multiple-dose trial. Results No serious adverse events were found in the study. In the single-dose trial, the testees showed no drug-related adverse reactions or abnormal changes in test patameters after the application of the creams. In the multiple-dose trial, no aberrant skin reaction or self-reported discomfort was noted in any of the testees from day 0 to 7 after the first initial application of the creams, but mild irritation occurred in 5 out of 6 volunteers applying the cream containing 0.2% tazarotene and 0.2% betamethasone dipropionate and in 2 out of 6 volunteers applying the cream containing 0.15% tazarotene and 0.15% betamethasone dipropionate on day 14, with no abnormal drug-related changes in the other test parameters. Conclusions The maximum tolerated concentration of both tazarotene and betamethasone dipropionate is 0.25% when they are topically applied in a combined cream for one session. It is relatively safe to apply the cream containing 0.15% tazarotene and 0.15% betamethasone dipropionate for 7 consecutive days. Key words: Skin; Haman body; External application drugs; Drug tolerance; Tazarotene betamethasone dipropionate cream

The Lipid-lowering Effects of R-bambuterol in Healthy Chinese Volunteers: A Randomized Phase I Clinical Study

BackgroundExisting treatments are inadequate for patients at high risk of coronary heart disease caused by elevated levels of plasma low-density lipoprotein cholesterol (LDL-C). Bambuterol is a prodrug of β2-agonist commonly used for the treatment of asthma and chronic obstructive pulmonary disease (COPD) with the advantage of once daily dosing and favorable side effect profile. The potential lipid-lowering effects of bambuterol were unclear, possibly due to the racemic bambuterol (rac-bambuterol) that was used in previous studies. MethodsThe lipid-lowering effects of R-bambuterol were examined in a randomized phase I trial in 48 healthy Chinese volunteers aged 18–45years. Participants were randomly assigned to five groups to receive a single dose (2.5mg, 5mg or 10mg) or multiple doses (5mg) of oral medications of R-bambuterol, or a single dose of rac-bambuterol (10mg). Plasma lipid levels were measured at baseline, time to peak concentration (Tmax) and 24h after the treatment. FindingsAdministration of a single-dose of R-bambuterol resulted in dose-dependent reductions in the levels of plasma LDL-C, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1) at Tmax. Levels of LDL-C exhibited the most reductions, which were statistically significant in all three single-dose R-bambuterol groups (all P values<0.05). R-bambuterol was more potent in LDL-C lowering compared to rac-bambuterol at Tmax (P=0.08). At 24h after dosing, the significant lipid lowering effects of R-bambuterol sustained for LDL-C (P=0.01), ApoB (P=0.001) and ApoA1 (P=0.03), but not for HDL-C. The ratio of ApoA1/ApoB was marginally increased (P=0.06). In the multiple-dose group, LDL-C levels again were significantly reduced (all P values<0.05), whereas the ratios of ApoA1/ApoB were marginally increased. InterpretationR-bambuterol can lower the plasma levels of LDL-C, and marginally raise the ratio of ApoA1/ApoB (indicator of HDL-C/LDL-C) with both a single dose and multiple doses. R-bambuterol was more potent in LDL-C lowering than rac-bambuterol.

The Effect of Phospholipids (Surfactant) on Adhesion and Biomechanical Properties of Tendon: A Rat Achilles Tendon Repair Model.

Adhesion of the tendon is a major challenge for the orthopedic surgeon during tendon repair. Manipulation of biological environment is one of the concepts to prevent adhesion. Lots of biochemicals have been studied for this purpose. We aimed to determine the effect of phospholipids on adhesion and biomechanical properties of tendon in an animal tendon repair model. Seventy-two Wistar rats were divided into 4 groups. Achilles tendons of rats were cut and repaired. Phospholipids were applied at two different dosages. Tendon adhesion was determined histopathologically and biomechanical test was performed. At macroscopic evaluation of adhesion, there are statistically significant differences between multiple-dose phospholipid injection group and Control group and also hyaluronic acid group and Control group (p < 0.008). At microscopic evaluation of adhesion, there was no statistically significant difference (p > 0.008). Ultimate strength was highest at hyaluronic acid injection group and lowest at multiple-dose phospholipid injection group. Single-dose phospholipids (surfactant) application may have a beneficial effect on the tendon adhesion. Although multiple applications of phospholipids seem the most effective regime to reduce the tendon adhesion among groups, it deteriorated the biomechanical properties of tendon.

Comparison between Micro-Dose GnRH Agonist and GnRH Antagonist Protocol in Poor Responders Undergoing Intracytoplasmic Sperm Injection with Embryo Transfer

Objective: To compare the effect of the multiple-dose GnRH antagonist protocol with the microdose GnRH agonist flare-up (MF) protocol in poor ovarian responders for ICSI. Design: Retrospective, Clinical study. Setting:IVF center. Patient(s): Two hundred eighty-six poor responder patients undergoing ICSI-embryo transfer cycle. Intervention(s): one hundred Forty four patients (144 cycles) included in group 1 (microdose GnRH-a flare-up protocol) and one hundred fourty two patients (42 cycles) included in group 2 (multiple dose GnRH antagonist protocol). Main Outcome Measure(s): Serum E2 levels, number of growing follicles and mature oocytes, embryo quality, dose of gonadotropin used, cancellation, fertilization, implantation rate, pregnancy rate (PR) and live birth rate (LR). Results: Total gonadotropin dose used was significantly lower (2730235,45 vs 3189317,81; P<0.05), duration of stimulation was significantly longer and E2 level was significantly higher in group 1. The mean number of oocytes retrived, mature oocytes retrived, embryos transferred and the rate of at least one top-quality embryo transferred was similar in the two groups. The implantation rate was significantly higher in the microdose flare-up group than in the multiple-dose antagonist group (18.79% vs 8.28%; P<.001). Clinical pregnancy and live birth rates were similar in the two groups. Conclusion(s): We achieved comparable pregnancy and live birth rates in poor responders with the use of either GnRH antagonist or flare protocol. However, a significantly higher gonadotropin dose used and lower implantation rate in the antagonist group tips the balance in favor of the flare-up protocol.

Pharmacokinetics and tolerability of the new second-generation nonnucleoside reverse- transcriptase inhibitor KM-023 in healthy subjects.

BackgroundKM-023 is a new second-generation nonnucleoside reverse-transcriptase inhibitor that is under development for the treatment of human immunodeficiency virus (HIV) type 1 infection.ObjectiveThis study determined KM-023 tolerability and pharmacokinetic characteristics in healthy subjects.Materials and methodsA randomized, double-blinded, placebo-controlled, dose-escalation study was conducted in 80 healthy South Korean male volunteers. The subjects were allocated to single- or multiple-dose (once daily for 7 days) groups that received 75, 150, 300, or 600 mg drug or placebo in a 4:1 ratio. Safety and pharmacokinetic assessments were performed during the study. Plasma and urine concentrations were quantified using liquid chromatography–tandem mass spectrometry.ResultsThe average maximum concentration (Cmax) and area under the concentration–time curve from time 0 to infinity (AUC∞) values of KM-023 for the 75–600 mg doses in the single-dose study ranged from 440.2 ng/mL to 1,245.4 ng/mL and 11,142.4 ng · h/mL to 33,705.6 ng · h/mL, respectively. Values of the mean Cmax at a steady state and AUC within the dosing interval ranged from 385.1 ng/mL to 1,096.7 ng/mL and 3,698.9 ng · h/mL to 10,232.6 ng · h/mL, respectively, following 75–600 mg doses in the multiple-dose study. Dose proportionality was not observed for KM-023. KM-023 showed a 0.6-fold accumulation after multiple doses in the 600 mg dose group. The mean half-life values ranged between 20.7 and 31.2 hours. KM-023 was generally well tolerated without serious adverse events.ConclusionKM-023 demonstrated dose- and time-dependent nonlinear pharmacokinetic characteristics after single or multiple doses over a dose range (75–600 mg) in healthy subjects. KM-023 showed favorable tolerability in this study. This Phase I clinical trial information can be used to design further clinical studies appropriately to evaluate KM-023 in patients with HIV-1 infection.

Exact Poly-K Test

For animal carcinogenicity study with multiple dose groups, positive trend test and pairwise comparisons of treated groups with control are generally performed using the Cochran-Armitage, Peto test, or Poly-K test. These tests are asymptotically normal. The exact version of Cochran-Armitage and Peto tests are available based on the permutation test assuming fixed column and row totals. For Poly-K test column totals depend on the mortality pattern of the animals and can not be kept fixed over the permutations of the animals. In this work a modification of the permutation test is suggested that can be applied on exact Poly-K test.

Integrated pharmacokinetics of five protoberberine-type alkaloids in normal and insomnic rats after single and multiple oral administration of Jiao-Tai-Wan

Ethnopharmacological relevanceJiao-Tai-Wan (JTW), an important herbal formula consists of Rhizoma coptidis and Cortex cinnamomi powder, is a famous prescription which has been used for centuries to treat insomnia in Traditional Chinese Medicine. The purpose of this study is to compare the pharmacokinetic properties of five protoberberine-type alkaloids (i.e. berberine, palmatine, coptisine, epiberberine and jatrorrhizine), the main bioactive constituents in JTW, between normal and insomnic rats. We also investigate the differences between single-dose and multiple-dose pharmacokinetics of five protoberberine-type alkaloids. Materials and methodsThe insomnic rat models were induced by intraperitoneal injection of one-dose para-chlorophenylalanine acid (PCPA). Quantification of five protoberberine-type alkaloids in rat plasma was achieved by using a rapid LC–MS/MS method. Plasma samples were collected at different time points to construct pharmacokinetic profiles by plotting drug concentration versus time and estimate pharmacokinetic parameters. An unpaired Student׳s t test was used for comparisons with SPSS 17.0. ResultsThe five protoberberine-type alkaloids of single-dose normal groups had slow absorption and low bioavailability, as well as a delay of peak time. In the single-dose oral administration, the Cmax and Tmax of five ingredients in insomnic rats had significant differences compared with those of normal rats. In the multiple-dose oral administration, the pharmacokinetic parameters of five protoberberine-type alkaloids varied greatly in insomnic rats. In the normal rats, there were significant differences (P<0.05) in the principal pharmacokinetic parameters such as Cmax and Tmax between single-dose and multiple-dose oral administration. In the insomnic rats, the five ingredients of multiple-dose groups showed better absorption than the single-dose groups. Particularly, three peaks were observed in multiple-dose model group of plasma–concentration curves. ConclusionsThe pharmacokinetic behavior of five protoberberine-type alkaloids was described in this paper. In both normal groups and model groups, the pharmacokinetic behavior of multiple-dose had significant differences comparing with the single-dose; either single-dose or multiple-dose, the pharmacokinetic behavior of insomnic rats had significant differences comparing the normal rats. Multiple dosing may improve the absorption of JTW in insomnic rats, which will increase the bioavailability and bring into active role in therapeutical effect.

English

AIMS AND OBJECTIVES: To compare if single dose antibiotic is as effective as multiple doses in prevention of post-operative infection in caesarean section. To compare the cost effectiveness of drugs in both the groups. MATERIAL AND METHOD: This prospective randomized controlled study was carried out to evaluate the effectiveness of single dose antibiotic versus multiple doses in caesarean section. The study population consisted of 600 patients that were randomly allocated to single or multiple dose groups. All potentially infected cases were excluded from this study. All patients received inj Cefotaxime IV half hour before surgery. In addition the multiple dose group received antibiotics for five days post-operatively. Each patient in the study was observed till discharge for presence of any morbidity like endometritis, urinary tract infections, and wound infections. STATISTICAL ANALYSISIS: Fischer exact test, unpaired t test used for analysis. RESULTS: There was no statistically significance in the rate of infections in both the groups. The rate of febrile morbidity, endometritis, urinary tract infection and wound infections were statistically not significant. However the difference in cost of antibiotic in both the groups was significant. CONCLUSIONS: Single dose antibiotics are effective as multiple doses in prevention of post-operative infections in caesarean sections Careful periodic surveillance of antibiotic prophylaxis is necessary to detect the emergence of drug resistant strains of bacteria in our institution because it caters to the

Predictors of success of different treatment modalities for management of ectopic pregnancy.

Aim. The purpose of this study was to investigate factors affecting the success of different treatment modalities for the management of ectopic pregnancy (EP). Methods. One hundred and ninety-seven patients with EP, were included in the study. Patients were treated with either intramuscular methotrexate (Mtx) or surgical treatment. Results. Mtx was applied in 97 (49.2%) patients. In 67 patients (69.1%), a single dose of Mtx and in 30 patients (30.9%) a multiple dose of Mtx was applied. Forty-seven (70.14%) patients were successfully treated with a single-dose Mtx. In the multiple-dose group, the success rate was 70% (21/30 patients). The difference between the success rates was not statistically significant. When the initial serum βhCG value was <1000 mIU/mL, the overall success rate of Mtx treatment was determined to be 86.11%; however, the rate decreased to 42.3% when the βhCG value was >3000 mIU/mL. On the other hand, if the EP mass diameter was <25 mm, the success rate was 89.28% and decreased to 52.63% when it was ≥25 mm. Conclusion. The results of the study showed that single-dose treatment with Mtx could be as successful as multiple doses. Overall success of Mtx treatment depended on initial βhCG value and EP mass diameter.

Modeling pharmacokinetics/pharmacodynamics of abatacept and disease progression in collagen-induced arthritic rats: a population approach

The PK/PD of abatacept, a selective T cell co-stimulation modulator, was examined in rats with collagen-induced arthritis (CIA) using a nonlinear mixed effect modeling approach. Male Lewis rats underwent collagen induction to produce rheumatoid arthritis. Two single-dose groups received either 10 mg/kg intravenous (IV) or 20 mg/kg subcutaneous (SC) abatacept, and one multiple-dose group received one 20 mg/kg SC abatacept dose and four additional 10 mg/kg SC doses. Effects on disease progression (DIS) were measured by paw swelling. Plasma concentrations of abatacept were assayed by enzyme-linked immunosorbent assay. The PK/PD data were sequentially fitted using NONMEM VI. Goodness-of-fit was assessed by objective functions and visual inspection of diagnostic plots. The PK of abatacept followed a two-compartment model with linear elimination. For SC doses, short-term zero-order absorption was assumed with F = 59.2 %. The disease progression component was an indirect response model with a time-dependent change in paw edema production rate constant (k in ) that was inhibited by abatacept. Variation in the PK data could be explained by inter-individual variability in clearance and central compartment volume (V 1 ), while the large variability of the PD data may be the result of paw edema production (k in 0 ) and loss rate constant (k out ). Abatacept has modest effects on paw swelling in CIA rats. The PK/PD profiles were well described by the proposed model and allowed evaluation of inter-individual variability on drug- and DIS-related parameters.

A phase 2, placebo-controlled, randomized, double-blind trial of tozadenant (Syn-115) in patients with Parkinson's disease with wearing-off fluctuations on levodopa

A phase 2, placebo-controlled, randomized, double-blind trial of tozadenant (Syn-115) in patients with Parkinson's disease with wearing-off fluctuations on levodopa

Recurrent Vertigo after Intratympanic Gentamicin for Ménière's Disease: Long‐term Follow‐up of Two Regimens

Objectives: 1) Analyze the recurrence rate of vertigo and the need for repeated injections of two different regimens of intratympanic gentamicin (ITG) (low dose and multiple daily dose). 2) Evaluate the efficacy of retreatment after long-term recurrence of vertigo attacks. Methods: We retrospectively analyzed 2 series of patients suffering from unilateral Ménière’s disease treated with low dose ITG (42) and multiple daily dose ITG (35) in a tertiary referral center. The mean period of follow-up was 4.8 years, and the outcome measurements were a) control of vertigo attacks, b) need of repeated treatment for recurrent vertigo evaluated using the Kaplan-Meyer method, and c) incidence of side effects (post-treatment dizziness, hearing loss). Results: At 2-year follow-up, complete control of vertigo was obtained with only 1 round of treatment in 30 (71%) low dose patients and 28 (80%) multiple daily dose patients. Side effects of ITG were significantly higher in the multiple daily dose group. At long-term follow-up (&gt; 4 years), the complete control vertigo rate decreased significantly, especially in the low dose group. 13 (31%) patients in the low dose group and 9 (25%) in the multiple daily dose group needed multiple rounds of treatment. Conclusions: Both regimen of ITG offered an excellent rate of vertigo control at 2-year follow-up. At long-term follow-up, the probability of recurrent vertigo attacks progressively increases, especially in the low dose group. The patients who experienced late recurrences of vertigo had less chance of achieving good results with additional rounds of ITG.

Pharmacokinetic properties of isradipine after single‐dose and multiple‐dose oral administration in Chinese volunteers: a randomized, open‐label, parallel‐group phase I study

Isradipine could be used for the treatment of high blood pressure or Parkinsonism, yet the study on pharmacokinetics (PK) of isradipine is lacking in the Chinese population. The current study aims to assess the dose proportionality, pharmacokinetics and gender effect of isradipine following oral single and multiple doses in Chinese subjects. A randomized, open-label, parallel-group trial was conducted in 30 healthy Chinese volunteers. Subjects randomly received a single dose of 2.5, 5 or 10 mg, and multiple doses (2.5 mg) of isradipine. Blood samples were collected pre-dose (0 h) and 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36 and 48 h post-dose. Isradipine was rapidly absorbed with the time to maximum concentration <1.27 h for all dosage groups. The maximum concentrations were 2.46, 5.34, 10.93 and 3.32 ng/mL and area under the concentration-time curve from time zero to the last time point (AUClast ) were 7.05, 12.58, 24.68 and 5.31 ng/ml · h for the 2.5, 5 and 10 mg single-dose and 2.5 mg multiple-dose groups, respectively. The half-life ranged from 5.76 to 7.94 h. The maximum concentration and AUC were found to increase linearly and dose-dependently for isradipine. No statistical gender differences were found. These findings indicated that the pharmacokinetic parameters of isradipine in Chinese population were dose-proportional and predictable over a range of 2.5-10 mg isradipine oral doses.