A bioequivalence study of two telmisartan 80 mg tablets in healthy Indonesian subjects: an open label, three-way, three-period, partial replicate crossover study

Paramanindita, Asti Swari; Harahap, Yahdiana; Prasaja, Budi; Wijayanti, Tri; Lusthom, Windy; Sofiah, Raden Efi; Sandra, Monika; Trisari, Yunia

doi:10.1080/03639045.2020.1820042

Cited by 3 publications

(2 citation statements)

References 11 publications

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“…23 The partial replicate design with 3 periods, including 2 administrations of the reference formulation in each sequence, provides the advantage of reducing the sample size of subjects required to demonstrate BE between the 2 formulations. 23 This design was also reported in the literature to assess the BE of highly variable drugs such as ibandronic acid, 23 telmisaratan, 24 and eperisone. 25 Employing a 3-sequence, 3-period, 2-treatment partially replicated crossover design was shown to offer greater practicality and efficiency compared with a 4-way, fully replicated crossover design.…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetics and Bioequivalence of Fixed‐Dose Combination of Simvastatin and Ezetimibe Tablets: A Randomized, Crossover, Open‐Label Study in Healthy Volunteers

Leong,

Yee,

Rani

et al. 2024

Clinical Pharm in Drug Dev

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The current study aimed to evaluate the bioequivalence of a new generic combination of simvastatin and ezetimibe with the reference formulation. An open‐label, randomized, 3‐period, 3‐sequence, crossover study, including 60 healthy volunteers, was implemented. Participants received the test and reference formulation, each containing 20 mg of simvastatin and 10 mg of ezetimibe as a single‐dose tablet, separated by a minimum of 2‐week washout periods. Blood samples were collected for 20 time points from predose to 72 hours after the dose. The total ezetimibe assay was carried out using a validated liquid chromatography‐tandem mass spectrometry, while unconjugated ezetimibe, simvastatin, and simvastatin β‐hydroxy acid determination was done via a validated ultra‐performance liquid chromatography‐tandem mass spectrometry. Each assay was preceded by a liquid‐liquid extraction step. The pharmacokinetic parameters were derived using noncompartmental analysis and then compared between the reference and test formulations via a multivariate analysis of variance. No statistical difference was found in under the concentration‐time curve from time 0 to the last quantifiable concentration and maximum concentration of unconjugated ezetimibe, total ezetimibe, and simvastatin between the reference and test formulations. The 90% confidence intervals of unconjugated ezetimibe, total ezetimibe, and simvastatin natural log‐transformed under the concentration‐time curve from time 0 to the last quantifiable concentration, and maximum concentration were in the range of 80%‐125% as per the bioequivalence acceptance criteria. Therefore, the test formulation was bioequivalent to the reference formulation.

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Section: Resultsmentioning

confidence: 99%

Pharmacokinetics and Bioequivalence of Fixed‐Dose Combination of Simvastatin and Ezetimibe Tablets: A Randomized, Crossover, Open‐Label Study in Healthy Volunteers

Leong,

Yee,

Rani

et al. 2024

Clinical Pharm in Drug Dev

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“…Данный подход описан Руководством по экспертизе лекарственных средств, Том 1 [9], руководством ЕАЭС [10]. Отметим, что авторы других опубликованных исследований биоэквивалентности также нередко сталкивались с необходимостью расширения ДИ для телмисартана [12][13][14][15].…”

Section: оценка биоэквивалентностиunclassified

Pharmacokinetic and bioequivalence study of Telzap® Plus fixed-dose combination compared with MikardisPlus® in healthy volunteers after single administration

Khokhlov

Мирошников

et al. 2023

Fk&Fd

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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.

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

Kubesh

Хохлов

Шитова³

et al. 2020

Razrabotka i registraciâ lekarstvennyh sredstv

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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.

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A bioequivalence study of two telmisartan 80 mg tablets in healthy Indonesian subjects: an open label, three-way, three-period, partial replicate crossover study

Cited by 3 publications

References 11 publications

Pharmacokinetics and Bioequivalence of Fixed‐Dose Combination of Simvastatin and Ezetimibe Tablets: A Randomized, Crossover, Open‐Label Study in Healthy Volunteers

Pharmacokinetics and Bioequivalence of Fixed‐Dose Combination of Simvastatin and Ezetimibe Tablets: A Randomized, Crossover, Open‐Label Study in Healthy Volunteers

Pharmacokinetic and bioequivalence study of Telzap® Plus fixed-dose combination compared with MikardisPlus® in healthy volunteers after single administration

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

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