Universität zu Köln

Siccardi, M., Almond, L., Schipani, A., Csajka, C., Marzolini, C., Wyen, C., Brockmeyer, N. H., Boffito, M., Owen, A. and Back, D. (2012). Pharmacokinetic and Pharmacodynamic Analysis of Efavirenz Dose Reduction Using an In Vitro-In Vivo Extrapolation Model. Clin. Pharmacol. Ther., 92 (4). S. 494 - 503. HOBOKEN: WILEY. ISSN 1532-6535

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Abstract

The pharmacokinetics (PK) of efavirenz (EFV) is characterized by marked interpatient variability that correlates with its pharmacodynamics (PD). In vitro in vivo extrapolation (IVIVE) is a bottom-up approach that combines drug data with system information to predict PK and PD. The aim of this study was to simulate EFV PK and PD after dose reductions. At the standard dose, the simulated probability was 80% for viral suppression and 28% for central nervous system (CNS) toxicity. After a dose reduction to 400 mg, the probabilities of viral suppression were reduced to 69, 75, and 82%, and those of CNS toxicity were 21, 24, and 29% for the 516 GG, 516 GT, and 516 TT genotypes, respectively. With reduction of the dose to 200 mg, the probabilities of viral suppression decreased to 54, 62, and 72% and those of CNS toxicity decreased to 13, 18, and 20% for the 516 GG, 516 GT, and 51611 genotypes, respectively. These findings indicate how dose reductions might be applied in patients with favorable genetic characteristics.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Siccardi, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Almond, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schipani, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Csajka, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Marzolini, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wyen, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brockmeyer, N. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boffito, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Owen, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Back, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-482270
DOI:	10.1038/clpt.2012.61
Journal or Publication Title:	Clin. Pharmacol. Ther.
Volume:	92
Number:	4
Page Range:	S. 494 - 503
Date:	2012
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1532-6535
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HIV-INFECTED PATIENTS; POPULATION PHARMACOKINETICS; DRUG ABSORPTION; PLASMA-CONCENTRATIONS; SECONDARY METABOLISM; ANTIVIRAL EFFICACY; CATALYTIC-ACTIVITY; HUMAN LIVER; CYP2B6; PREDICTION Multiple languages Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48227