Pharmacokinetics of fixed-dose combination of tenofovir disoproxil fumarate, lamivudine, and efavirenz: results of a randomized, crossover, bioequivalence study

2016 ◽  
Vol 28 (5) ◽  
pp. 491-498 ◽  
Author(s):  
Dhiraj Abhyankar ◽  
Ashish Shedage ◽  
Milind Gole ◽  
Preeti Raut
Keyword(s):  
Tenofovir Disoproxil Fumarate ◽  
Geometric Mean ◽  
Bioequivalence Study ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Geometric Mean Ratio ◽  
Open Label ◽  
Post Dose ◽  
Dose Combination ◽  
The Individual

The objective of this study was to assess the bioequivalence between a fixed-dose combination of tenofovir disoproxil fumarate/lamivudine/efavirenz 300/300/600 mg and the individual innovator products. A randomized, balanced, open-label, two-sequence, two-treatment, two-period, single dose, crossover study in 48 healthy adults was conducted. Dosing was separated by a washout period of 32 days. Twenty-seven blood samples were collected in each period from pre-dose to 72 h post-dose. The data of 45 subjects were analyzed for pharmacokinetics and safety. Ninety percent CIs of geometric mean ratio on Cmax, AUC0–t, and AUC0-inf for tenofovir and lamivudine and on Cmax and AUC0-72 for efavirenz were within the acceptance criteria (80–125%). For tenofovir disoproxil fumarate, the Tmax, Kel, and t1/2 values for the test and reference products were 1.02 versus 0.91 h, 0.04 versus 0.04/h, 18.67 versus 18.46 h, respectively. For lamivudine, the Tmax, Kel, and t1/2 values were: 1.38 versus 1.30 h, 0.21 versus 0.19/h, 3.44 versus 3.91 h, respectively. For efavirenz, the Tmax values for the test and reference products were 3.71 and 3.65 h, respectively. Both the treatments were well tolerated. Our findings suggest that the tested formulation is bioequivalent to the innovators’ formulations, and both treatments were well tolerated.

scholarly journals Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate administered as an inhaled fixed-dose combination in Japanese and Caucasian healthy subjects

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Satoru Inoue ◽  
Soniya Vaidya ◽  
Hanns-Christian Tillmann ◽  
Yohei Sakita ◽  
Surendra Machineni ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Mometasone Furoate ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
High Dose ◽  
Open Label ◽  
Post Dose ◽  
Glycopyrronium Bromide ◽  
Dose Combination ◽  
Medium Dose

Abstract Background A once-daily (o.d.) fixed-dose combination of indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF) delivered via the Breezhaler® device (IND/GLY/MF) is being developed for treatment of asthma. This study compared steady-state pharmacokinetics of IND, GLY and MF between Japanese and Caucasian male subjects after multiple inhalations of IND/GLY/MF o.d. Methods This was a single-center, open-label, 2-treatment crossover study with a 21-day washout period. Japanese and Caucasian subjects received IND/GLY/MF 150/50/80 μg (inhaled corticosteroid [ICS] medium-dose) or 150/50/160 μg o.d. (ICS high-dose) for 14 days in each period. Pharmacokinetics were characterized up to 24 h post-dose on Days 1 and 14. Results In total, 16 Japanese (median age 31 years [range 20–40 years], mean weight 68.3 kg) and 17 Caucasian subjects (median age 27 years [range 21–43 years], mean weight 75.0 kg) were randomized. Geometric mean ratios (Japanese/Caucasian) [90% confidence interval (CI)] for Cmax for IND, GLY and MF at the high ICS dose on Day 14 were 1.31 [1.13, 1.51] 1.38 [1.13, 1.69] and 1.07 [0.969, 1.18], respectively. Geometric mean ratios (Japanese/Caucasian) [90% CI] for AUC0–24h on Day 14 for IND, GLY and MF at the high ICS dose were 1.17 [1.01, 1.35], 1.05 [0.920, 1.20] and 1.15 [1.05, 1.27] respectively. Similar trends were noted for all components for the medium ICS dose treatment. IND/GLY/MF was safe and well tolerated; no AEs suspected to be study drug-related were observed. Conclusion Pharmacokinetics of IND, GLY and MF (high and medium dose) when delivered as a fixed-dose combination were comparable between Japanese and Caucasian subjects. The IND/GLY/MF combination at the administrated doses was safe and well tolerated in both ethnic groups. Trial registration Japan Registry of Clinical Trial: jRCT2031200227, retrospectively registered on 04, December, 2020.

scholarly journals A Replicate Designed Bioequivalence Study To Compare Two Fixed-Dose Combination Products of Artesunate and Amodiaquine in Healthy Chinese Volunteers

2014 ◽  
Vol 58 (10) ◽  
pp. 6009-6015 ◽  
Author(s):  
Yun Liu ◽  
Chaoying Hu ◽  
Gangyi Liu ◽  
Jingying Jia ◽  
Chen Yu ◽  
...  
Keyword(s):  
Confidence Intervals ◽  
Geometric Mean ◽  
Bioequivalence Study ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Sample Collection ◽  
Intrasubject Variability ◽  
Time Curve ◽  
Coefficients Of Variation ◽  
Dose Combination

ABSTRACTArtesun-Plus is a fixed-dose combination antimalarial agent containing artesunate and amodiaquine. The current study was conducted to compare the pharmacokinetic and safety profiles of Artesun-Plus and the WHO-designated comparator product Artesunate Amodiaquine Winthrop. To overcome the high intrasubject variability of artesunate, the study applied a two-sequence and four-period crossover (2 by 4), replicate study design to assess bioequivalence between the two products in 31 healthy male Chinese volunteers under fasting conditions. The results showed that the values of the geometric mean ratios of maximum concentration of drug in plasma (Cmax) and area under the concentration-time curve from time zero to the last blood sample collection (AUC0-last) for the artesunate component in the test and reference products were 95.9% and 93.9%, respectively, and that the corresponding 90% confidence intervals were 84.5% to 108.7% and 87.2% to 101.1%, while the geometric mean ratios for the amodiaquine component in the test and reference products were 95.0% and 100.0%, respectively, and the corresponding 90% confidence intervals were 86.7% to 104.1% and 93.5% to 107.0%. In conclusion, bioequivalence between the two artesunate and amodiaquine fixed-dose combination products was demonstrated for both components. The study also confirmed high intrasubject variability, especially for artesunate: the coefficients of variation (CV) ofCmaxvalues for the test and reference products were 39.2% and 43.7%, respectively, while those for amodiaquine were 30.6% and 30.2%, respectively.

scholarly journals Pharmacokinetic and Bioequivalence Study of Telzap AM® (Telmisartan/amlodipine Fixed-dose Combination) and Coadministered Mikardis® (Telmisartan) and Norvask® (Amlodipine) in Healthy Subjects

2020 ◽  
Vol 9 (4) ◽  
pp. 155-163
Author(s):  
V. Kubesh ◽  
A. L. Khokhlov ◽  
A. M. Shitova ◽  
Yu. A. Dzhurko ◽  
V. I. Kazey ◽  
...  
Keyword(s):  
Confidence Intervals ◽  
Drug Product ◽  
Bioequivalence Study ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Combination Drug ◽  
Drug Products ◽  
Dose Combination

Introduction. A fixed dose combination of telmisartan and amlodipine is widely used in clinical practice during hypertension treatment. Combination of telmisartan and amlodipine demonstrates potentiating synergistic effect on blood pressure decrease. A bioequivalence study of Telzap® AM with coadministered Mikardis® and Norvask® was conducted with 60 volunteers.Aim. The purpose of the bioequivalence trial was a comparative study of the pharmacokinetics and evidence of the bioequivalence of the fixed dose combination drug product Telzap® AM (telmisartan + amlodipine, tablets, 80 + 10 mg, Zentiva ks company, Czech Republic) and coadministrated monocomponent drug products Mikardis® (telmisartan, tablets 80 mg, Beringer Ingelheim International GmbH, Germany) and Norvask® [amlodipine, tablets 10 mg, Pfizer HCP Corporation (USA), Russia] in healthy volunteers after a single administration under fasting.Materials and methods. To prove bioequivalence, an open label, comparative, randomized, crossover four-period replicate clinical trial was conducted. The concentrations of amlodipine and telmisartan in plasma samples were determined by a validated HPLC-MS/MS method. A pharmacokinetic and statistical analysis was performed and confidence intervals for the pharmacokinetic parameters Cmax and AUC0-72 were calculated.Results and discussion. It can be concluded that the studied formulations are bioequivalent in terms of pharmacokinetic parameters of amlodipine and telmisartan. All 90 % confidence intervals for the estimated pharmacokinetic parameters of amlodipine were in the range of 80–125 %, 90 % confidence intervals for telmisartan were within the bioequivalence range of 80–125 % for AUC0-72, and 76.73–130.32 % for Cmax.Conclusion. Thus, according to the criteria used in the study, the formulations are proved to be bioequivalent.

scholarly journals Management of peripheral neuropathy symptoms with a fixed dose combination of high-dose vitamin B1, B6 and B12: A 12-week prospective non-interventional study in Indonesia

2018 ◽  
Vol 9 (1) ◽  
pp. 32-40 ◽  
Author(s):  
Manfaluthy Hakim ◽  
Nani Kurniani ◽  
Rizaldy Taslim Pinzon ◽  
Dodik Tugasworo ◽  
Mudjiani Basuki ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Peripheral Neuropathy ◽  
Vitamin B1 ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
High Dose ◽  
Clinical Trial Registry ◽  
Open Label ◽  
Dose Combination

Background: Peripheral neuropathy is a common condition which can have a significant impact on quality of life. It occurs as a component of several common and rare diseases or can be idiopathic and can present with various symptoms.Aims and Objectives: This study is aimed at evaluating the effectiveness and safety of the fixed dose combination of vitamin B1, B6 and B12in mild to moderate peripheral neuropathy of various etiologies in the Indonesian population.Materials and Methods: This was a prospective, open label, multi-center, single arm observational study (Indonesian Clinical Trial Registry No: INA-KPA0DYA). A total of 411 subjects with mild to moderate peripheral neuropathy of various etiologies, who met the eligibility criteria, were included in the study. A subject was considered to have “completed” the study if the study procedures, up to Visit 3 (one month of treatment) were accomplished. Procedural results and 12-week clinical outcomes are reported.Results: Treatment with combination of vitamin B1, B6 and B12 in subjects with symptoms of PN showed significant improvement in overall Total Symptom Score (TSS), within 14 days. The treatment also successfully reduced individual components of TSS from baseline to Visit 5. A significant percentage reduction was also observed for all the Visual Analogue Scale (VAS) parameters at the end of 12 weeks, while the Quality of Life (QoL) scores increased from baseline to the end of treatment.Conclusions: The fixed dose combination of vitamin B1, B6 and B12 was effective and welltolerated in subjects with mild to moderate peripheral neuropathy, of various etiologies.Asian Journal of Medical Sciences Vol.9(1) 2018 32-40

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