Human physiologically based pharmacokinetic model for ACE inhibitors: ramipril and ramiprilat.

ABSTRACT:

Background

The angiotensin-converting enzyme (ACE) inhibitors have complicated and poorly characterized pharmacokinetics. There are two binding sites per ACE (high affinity "C", lower affinity "N") that have sub-nanomolar affinities and dissociation rates of hours. Most inhibitors are given orally in a prodrug form that is systemically converted to the active form. This paper describes the first human physiologically based pharmacokinetic (PBPK) model of this drug class.

Methods

The model was applied to the experimental data of van Griensven et. al for the pharmacokinetics of ramiprilat and its prodrug ramipril. It describes the time course of the inhibition of the N and C ACE sites in plasma and the different tissues. The model includes: 1) two independent ACE binding sites

SUBMITTER: Levitt DG 

PROVIDER: S-EPMC1373666 | biostudies-literature | 2006 Jan

REPOSITORIES: biostudies-literature