A Comparative Single Dose Bioequivalence Study of Extended Release Antihypertensive Drug Formulation among Healthy Human Volunteers

Abstract

The objective of this study was to compare the in vivo characteristics of diltiazem extended release formulations for once daily, which were expected to be bioequivalent. Either two capsules of a test formulation or a 1 of the reference formulation, both containing 360 mg diltiazem were administered to healthy male volunteers after keeping fast of ten hour in a randomized, open label,three period crossover design. Plasma samples obtained over the subsequent period of 72 hours were analyzed using a validated LC-MS/MS method. Safety profile and tolerability of the study medications were assessed by analysis of adverse events obtained by vital sign measurements, electrocardiography, and clinical. The 90% CI for the log transformed data for Cmax, AUC0-t,AUC0-∞ for both the test product fell in the prescribed limits of bioequivalence for narrow therapeutics index drugs i.e. 80 to 120%. This single dose study found that the test and reference products met the regulatory criteria for bioequivalence in healthy, male volunteers under fasting

Keywords

• Diltiazem, bioequivalence, bioavailability

A Comparative Single Dose Bioequivalence Study of Extended Release Antihypertensive Drug Formulation among Healthy Human Volunteers

Öz

Bu çalışmanın amacı, biyolojik olarak eşdeğer olması beklenen, günde bir defalık diltiazem uzatılmış salınım formülasyonlarının in vivo özellikleri karşılaştırmaktı. Her ikisi de 360 mg Diltiazem ihtiva eden bir test formülasyonun iki kapsülü veya referans formülasyonun 1 kapsülü, on saat aç bekletildikten sonra sağlıklı erkek gönüllülere randomize, açık etiketli, üç periyotlu çapraz tasarımda verilmiştir. Üzerinden 72 saat süre geçtikten sonra elde edilen Plazma numuneleri geçerli bir LC-MS/MS yöntemi kullanılarak analiz edildi. Çalışma ilaçlarının güvenlik profili ve tolere edilebilirliği vital bulguların ölçümü, elektrokardiyografi ve klinik ile elde edilen yan etkilerin analizi ile değerlendirildi. Cmax log dönüştürülmüş verileri için 90% CI, AUC0-t,AUC0-∞ her iki ilaç için dar terapötik indeks ilaçlar için biyoeşdeğerliliğin öngörülen limitleri içine düştü, örneğin 80- 120%. Bu tek doz çalışma tespit etmiştir ki test ve referans ürünler açlık altında sağlıklı, erkek gönüllülerde biyoeşdeğerlik için düzenleyici kriterleri karşılamaktadır

Anahtar Kelimeler

• Diltiazem, biyoeşdeğerlik, biyoyararlanım

Kaynakça

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