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Prediction of metabolic drug clearance in humans: in vitro-in vivo extrapolation vs allometric scaling.
Shiran, M R; Proctor, N J; Howgate, E M; Rowland-Yeo, K; Tucker, G T; Rostami-Hodjegan, A.
Afiliación
  • Shiran MR; Academic Unit of Clinical Pharmacology, Division of Clinical Sciences (South), University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK.
Xenobiotica ; 36(7): 567-80, 2006 Jul.
Article en En | MEDLINE | ID: mdl-16864504
Previously in vitro-in vivo extrapolation (IVIVE) with the Simcyp Clearance and Interaction Simulator has been used to predict the clearance of 15 clinically used drugs in humans. The criteria for the selection of the drugs were that they are used as probes for the activity of specific cytochromes P450 (CYPs) or have a single CYP isoform as the major or sole contributor to their metabolism and that they do not exhibit non-linear kinetics in vivo. Where data were available for the clearance of the drugs in at least three animal species, the predictions from IVIVE have now been compared with those based on allometric scaling (AS). Adequate data were available for estimating oral clearance (CLp.o.) in 9 cases (alprazolam, sildenafil, caffeine, clozapine, cyclosporine, dextromethorphan, midazolam, omeprazole and tolbutamide) and intravenous clearance in 6 cases (CLi.v.) (cyclosporine, diclofenac, midazolam, omeprazole, theophylline and tolterodine). AS predictions were based on five different methods: (1) simple allometry (clearance versus body weight); (2) correction for maximum life-span potential (CL x MLP); (3) correction for brain weight (CL x BrW); (4) the use of body surface area; and (5) the rule of exponents. A prediction accuracy was indicated by mean-fold error and the Pearson product moment correlation coefficient. Predictions were considered successful if the mean-fold error was
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Preparaciones Farmacéuticas Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Xenobiotica Año: 2006 Tipo del documento: Article Pais de publicación: Reino Unido
Buscar en Google
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Imprimir
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PubMed Links

Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Preparaciones Farmacéuticas Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Xenobiotica Año: 2006 Tipo del documento: Article Pais de publicación: Reino Unido