RE: Multiple dose analysis using NONMEM

From: "Anthe Zandvliet" Apaza@slz.nl Subject: RE: [NMusers] Multiple dose analysis using NONMEM Date: Mon, 10 Jul 2006 10:37:52 +0200 Dear Vipul, Please take a look at the references below. Iphosphamide and cyclophosphamide autoinduction have been modeled using an enzyme turnover model. In these models, the elimination of the hypothetical enzyme is decreased during exposure to iphosphamide or cyclophosphamide. In order to model autoinhibition, you may consider using this model with a decreased input of the enzyme during drug exposure. Various effect functions are possible (e.g. iphosphamide: Emax, cyclophosphamide:on/off). Anthe references: Kerbusch T, Huitema ADR, Ouwerkerk J, et al: Evaluation of the autoinduction of ifosfamide metabolism by a population pharmacokinetic approach using NONMEM. Br J Clin Pharmacol 49:555-561, 2000 de Jonge ME, Huitema ADR, Rodenhuis S, et al: Integrated Population Pharmacokinetic Model of both cyclophosphamide and thiotepa suggesting a mutual drug-drug interaction. J Pharmacokinet Pharmacodyn 31:135-156, 2004 Anthe Zandvliet Slotervaart Hospital Dept. Pharmacy and Pharmacology Louwesweg 6 1066 EC AMSTERDAM The Netherlands Telephone +31 20 512 4657 FAX + 31 20 512 4753