In Vitro-In Vivo Correlations Based on In Vitro Dissolution of Parent Drug Diltiazem and Pharmacokinetics of Its Metabolite

被引：18

作者：

Mircioiu, Constantin ^{[1
]}

Anuta, Valentina ^{[2
]}

Mircioiu, Ion ^{[3
]}

Nicolescu, Adrian ^{[4
]}

Fotaki, Nikoletta ^{[5
]}

机构：

[1] Carol Davila Univ Med & Pharm, Fac Pharm, Dept Appl Math & Biostat, Bucharest 020956, Romania

[2] Carol Davila Univ Med & Pharm, Fac Pharm, Dept Phys & Colloidal Chem, Bucharest 020956, Romania

[3] Titu Maiorescu Univ, Dept Biopharm & Pharmacokinet, Bucharest 004051, Romania

[4] Queens Univ, Dept Med, Kingston, ON K7L 3N6, Canada

[5] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England

来源：

PHARMACEUTICS | 2019年 / 11卷 / 07期

关键词：

in vitro-in vivo correlation (IVIVC); diltiazem; mathematical modeling; metabolites; dissolution; RELEASE; MODEL; TABLETS; CIRCULATION; VALIDATION; RIFAMPICIN; LEVEL;

D O I：

10.3390/pharmaceutics11070344

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

In this study a novel type of in vitro-in vivo correlation (IVIVC) is proposed: The correlation of the in vitro parent drug dissolution data with the in vivo pharmacokinetic data of drug's metabolite after the oral administration of the parent drug. The pharmacokinetic data for the parent drug diltiazem (DTZ) and its desacetyl diltiazem metabolite (DTZM) were obtained from an in vivo study performed in 19 healthy volunteers. The pharmacokinetics of the parent drug and its metabolite followed a pseudomono-compartmental model and deconvolution of the DTZ or DTZM plasma concentration profiles was performed with a Wagner-Nelson-type equation. The calculated in vivo absorption fractions were correlated with the in vitro DTZ dissolution data obtained with USP 2 apparatus. A linear IVIVC was obtained for both DTZ and DTZM, with a better correlation observed for the case of the metabolite. This type of correlation of the in vitro data of the parent compound with the in vivo data of the metabolite could be useful for the development of drugs with active metabolites and prodrugs.

引用

页数：15

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