Re: Multiple dose analysis using NONMEM

From: tgordi@buffalo.edu Subject: Re: [NMusers] Multiple dose analysis using NONMEM Date: Tue, 11 Jul 2006 20:02:56 -0400 Dear Vipul, I would like to suggest a look at the following paper: Gordi T, Xie R, Huong NV, Huong DX, Karlsson MO, Ashton M.: A semiphysiological pharmacokinetic model for artemisinin in healthy subjects incorporating autoinduction of metabolism and saturable first-pass hepatic extraction. Br J Clin Pharmacol. 2005 Feb;59(2):189-98 where we modeled the autoinduction of artemisinin using saliva samples, allowing drug liver amounts to increase the production rate of an enzyme precursor compartment. Enzyme amounts were then correlated directly to the CLin, which using a well-stirred model, resulted in increased extraction degree (EH) of the compound. EH was then related to both total CL and F. The model can be applied to other conditions, such as autoinhibition or changes in f due to displacement. The model performed satisfactorily when applied to another set of limited saliva data (Gordi T, Xie R, Jusko WJ. Br J Clin Pharmacol. 2005 Dec;60(6):594-604) and has done very well in describing the autoinduction of artemisinin in plasma samples from 6 previous studies (manuscript under way). Toufigh Gordi _______________________________________________________