Introduction. A fixed dose combination of telmisartan and hydrochlorothiazide is indicated for treatment of in the treatment of arterial hypertension. The combination of these substances causes an additive effect that helps to reduce blood pressure. A bioequivalence study of Telzap® Plus compared with MikardisPlus® was conducted with 63 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® Plus (tablets 80 mg + 12,5 mg, Zentiva KS company, Czech Republic) compared with drug products MikardisPlus® (telmisartan+hydrochlorothiazide, tablets 80 mg + 12,5 mg, Boehringer Ingelheim Pharma GmbH & Co. KG, Germany) in healthy volunteers after a single administration under fasting.Materials and methods. To prove bioequivalence, an open label, comparative, randomized, crossover fourperiod replicate single-center clinical trial was conducted. The concentrations of hydrochlorothiazide and telmisartan in plasma samples were determined with 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 hydrochlorothiazide and telmisartan. All 90 % confidence intervals for the estimated pharmacokinetic parameters of hydrochlorothiazide were in the range of 80–125 %, 90 % confidence intervals for telmisartan were within the bioequivalence range of 80–125 % for AUC0-72, and 79,30–126,11 % for Cmax.Conclusion. Thus, according to the criteria used in the study, the formulations are proved to be bioequivalent.

Introduction. Telmisartan is widely used in clinical practice during hypertension treatment. It is a specific angiotensin II receptor antagonist (type AT1), effective at oral intake, A bioequivalence study of Telzap® and Mikardis® 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 Mikardis® (telmisartan, tablets 80 mg, Boehringer Ingelheim International GmbH, Germany) and Telzap® (telmisartan, tablets 80 mg, Zentiva KS company, Czech Republic) in healthy volunteers after a single administration under fasting.Materials and methods. To prove bioequivalence, an open label, comparative, randomized, crossover four-period replicate single-center clinical trial was conducted. The concentrations of 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 test and reference drug. All 90 % confidence intervals of were within the bioequivalence range of 80–125 % for AUC0-72 and 73,07–136,85 % for Cmax.Conclusion. Thus, according to the criteria used in the study, the formulations are proved to be bioequivalent.

Introduction. The advantages of fixed-dose combination losartan + amlodipine + rosuvastatin compared to mono-drugs and two-component combinations are to increase the therapeutic efficacy, to reduce the cost of the product and to make the drug easier to take which helps to improve patient adherence to therapy. A bioequivalence study of the three-component fixed-dose combinations Losartan + amlodipine + rosuvastatin Sanofi with coadministered Lozap® AM (Losartan+Amlodipine) and Crestor® (Rosuvastatin) was conducted.   Aim. The purpose of the bioequivalence trial was a comparative study of the pharmacokinetics and evidence of the bioequivalence of two strengths of fixed-dose combination: 1) Losartan + amlodipine + rosuvastatin Sanofi (tablets, 50 mg + 5 mg + 10 mg) in comparison with coadministrated drugs Lozap® AM (losartan + amlodipine, tablets, 50 mg + 5 mg,) and Crestor® (rosuvastatin, tablets, 10 mg) in fasting healthy volunteers after a single administration; 2) Losartan + amlodipine + rosuvastatin Sanofi (tablets, 100 mg + 5 mg + 20 mg) in comparison with coadministrated drugs Lozap® AM (losartan + amlodipine, tablets, 100 mg + 5 mg) and Crestor® (rosuvastatin, tablets, 20 mg) in fasting healthy volunteers 18–45 years old after a single dose.   Materials and methods. To prove bioequivalence, an open label, comparative, randomized, crossover four-period clinical trial was conducted for each strengths of fixed-dose combination. The concentrations of losartan, amlodipine and rosuvastatin in blood plasma samples obtained from volunteers were determined by a validated HPLC-MS/MS method. A pharmacokinetic and statistical analysis was performed and confidence intervals (CI) for the pharmacokinetic parameters Сmax, AUC0-72 (for amlodipine) and AUC0-t (for losartan and rosuvastatin) were calculated.      Results and discussion. Based on the results of statistical and pharmacokinetic analysis, it was shown that the studied formulations are bioequivalent in terms of pharmacokinetic parameters of losartan, amlodipine and rosuvastatin. 90 % CI were in the acceptable range for Сmax (of amlodipine), AUC0-72 (of amlodipine) and AUC0-t (of losartan and rosuvastatin). 90 % CI for Сmax of losartan and rosuvastatin were in the acceptable extended calculated range according to the protocol.   Conclusion. Thus, according to the criteria used in the studies, the three-component fixed-dose combinations Losartan + amlodipine + rosuvastatin Sanofi are proved to be bioequivalent in comparison with coadministered Lozap® AM and Crestor®.

Objective: Drug Amlodipine+Valsartan is safe and effective for comprehensive treatment of arterial hypertension patients taken combined therapy by prescription. The development of new fix drug combination amlodipine and valsartan will provide in the near future a significant reduction in the cost of treatment. The aim of this work was investigation of bioequivalence for a generic drug Amlodipine+Valsartan, film-coated tablets, 10 mg+160 mg (Polpharma SA, Poland) and Exforge®, film-coated tablets, 10 mg+160 mg (Novartis Pharma AG, Switzerland). Materials and methods: 58 healthy volunteers were enrolled in open label, randomized, two sequence, two treatment cross-over study. Drugs were administered in two periods with a 21-day washout period in-between. Blood samples were collected over a 72-hour period. Amlodipine and Valsartan were measured in plasma using an automated LC-MS/MS assay. Pharmacokinetic parameters were calculated by non-compartmental analyses approach to evaluate AUC0-t, AUC0-∞ and Cmax. ANOVA was performed on the ln-transformed data and the 90% Confidence Interval (CI) was determined. Bioequivalence will be concluded if the 90% CI falls within 80-125% for AUC0-t and Cmax. Results: 53 volunteers completed the study and were considered for the pharmacokinetic and statistical analyses. Descriptive safety data analyses were performed on all 58 subjects. 90%-CI for corrected GMEAN of test and reference ratio was 94.76-105.24% for AUC0-t and 92.78-108.79% for Cmax in the case of amlodipine; 94.93-119.61% for AUC0-t and 90.41-116.03% for Cmax in the case of valsartan. So all pharmacokinetic parameters met the acceptance criteria as the 90% CI were within 80.00-125.00%. Conclusion: This study showed that Amlodipine+Valsartan, film-coated tablets, 10 mg+160 mg (Polpharma SA, Poland) is bioequivalent to reference product Exforge®, film-coated tablets, 10 mg+160 mg (Novartis Pharma AG, Switzerland).

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.