𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Inhibition-based metabolic drug–drug interactions: Predictions from in vitro data

✍ Scribed by Caiping Yao; René H. Levy

Publisher
John Wiley and Sons
Year
2002
Tongue
English
Weight
132 KB
Volume
91
Category
Article
ISSN
0022-3549

No coin nor oath required. For personal study only.

✦ Synopsis

There has been a growing interest in predicting in vivo metabolic drug-drug interactions from in vitro systems. High-throughput screening methods aimed at assessing the potential of drug candidates for drug interactions are widely used in industry. However, at present, there is no consensus on methodologies that would yield reliable quantitative predictions, because a number of issues remain unsolved, such as estimations of inhibition constants in vitro and inhibitor concentration around the enzyme site in vivo. In the present review, different approaches to estimation of inhibitor concentration around the enzyme site are summarized; also, the problems associated with estimation of in vitro K(i) values due to incubation conditions and environment differences between in vitro and in vivo are presented. A new approach based on comparisons of in vitro and in vivo inhibition potencies by calculation of in vivo inhibition constants is discussed. Examples of predictions of in vivo drug interactions based on mechanism-based inactivation are described. Unresolved issues that would allow further refinement of existing prediction models are also evaluated.

📜 SIMILAR VOLUMES

Prediction of plasma protein binding dis
Prediction of plasma protein binding displacement and its implications for quantitative assessment of metabolic drug–drug interactions from in vitro data
✍ Hege Christensen; Mark Baker; Geoffrey T. Tucker; Amin Rostami-Hodjegan 📂 Article 📅 2006 🏛 John Wiley and Sons 🌐 English ⚖ 231 KB 👁 1 views

Although displacement from plasma protein binding (dPB) is usually of little clinical significance, it should be taken into account when interpreting changes in total plasma concentrations of drugs subject to metabolically based drug-drug interactions (mDDI). The aim of this study was to develop an

Prediction of drug distribution in vivo
Prediction of drug distribution in vivo on the basis of in vitro binding data
✍ G. Schuhmann; B. Fichtl; H. Kurz 📂 Article 📅 1987 🏛 John Wiley and Sons 🌐 English ⚖ 630 KB

For 11 drugs it was investigated whether tissue distribution in vivo can be predicted by use of binding data obtained in vitro. The selection of drugs represented a broad spectrum of physicochemical and pharmacokinetic properties thought to be important for distribution of drugs in vivo. The extent

Predicting human drug pharmacokinetics f
Predicting human drug pharmacokinetics from in vitro permeability using an absorption–disposition model
✍ Kyle A. Fliszar; Brian T. Hill; Natalie Foster 📂 Article 📅 2007 🏛 John Wiley and Sons 🌐 English ⚖ 295 KB

The purpose of this research is to simulate the in vivo performance of drugs with a wide range of solubility and permeability characteristics formulated as oral dosage forms. The absorption-disposition model was developed using a number of physiological parameters as well as in vitro permeability da