当前位置： SCI文献检索 > CLINICAL PHARMACOKINETICS期刊下所有文献 > Biowaivers for oral immediate-release products: implications of linear pharmacokinetics.

Biowaivers for oral immediate-release products: implications of linear pharmacokinetics.

Abstract：

:Bioequivalence of drug formulations plays an important role in drug development. Recently, the Biopharmaceutical Classification System (BCS) has been implemented for the purpose of waiving bioequivalence studies on the basis of the solubility and gastrointestinal permeability of drug substance. Using the rationale of the BCS, it can be argued that biowaivers can, however, also be granted on the basis of standard pharmacokinetic data. If a drug exhibits dose-linear pharmacokinetics and a sufficiently fast dissolution profile, it can be concluded that this drug appears to pose no problem with respect to absorption. It should be noted that a change of an immediate-release tablet formulation can only lead to a deviating rate and/or extent of absorption when release of the drug from the formulation is altered. Logically, the dissolution profiles of the different formulations should be equal to guarantee bioequivalency. Thus, both BCS and the alternative linear pharmacokinetics approach require an evaluation of dissolution profiles. The justification of BCS is found in the permeability classification of the compound, while those of the linear pharmacokinetics lie in the apparent lack of a permeability problem. For example, in this context P-glycoprotein-transported drugs form an interesting class of compounds, which may be treated likewise when complying to the aforementioned requirements. Furthermore, poorly soluble compounds may be less troublesome than expected. It is shown that linear kinetics can be explained by the solubilising activity of, for example, bile salts. In this instance, linear pharmacokinetics shows that elevated doses do not appear to exhibit a limiting role on the dissolution. Hence, a change in formulation without any effect on the dissolution profile is not expected to cause a change in availability. It is clear that the formulations to be compared should not contain excipients that display an effect on (presystemic) drug metabolism.

journal_name

Clin Pharmacokinet

journal_title

Clinical pharmacokinetics

authors

Faassen F,Vromans H

doi

10.2165/00003088-200443150-00004

keywords:

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

1117-26

issue

eissn

0312-5963

issn

1179-1926

pii

43154

journal_volume

pub_type

杂志文章,评审

在线工具

Biowaivers for oral immediate-release products: implications of linear pharmacokinetics.