flip-flop kinetics

From: "Bonate, Peter, Quintiles" <pbonate@qkcm.quintiles.com> Subject: flip-flop kinetics Date: Fri, 2 Apr 1999 10:23:52 -0600 I have never had occassion to model a drug with flip-flop kinetics before. I understand that if you model a one-compartment system as C=A*exp(-alpha*t)+B*exp(-beta*t) then you have to assume that Ka>Kel. But what if you model a system as a series of differential equations: dX1/dt = -Ka*X1 dX2/dt = Ka*X1 - Kel*X2 with scaling parameter C=X2/V? Are the output rate constants from such a fit really the right values? The standard errors are quite precise and the fit appears excellent. Unfortunately, I do not have iv data. Any comments on this would be appreciated. Thanks. PETER L. BONATE, PhD. Clinical Pharmacokinetics Quintiles POB 9708 (L4-M2828) Kansas City, MO 64134 phone: 816-767-6084 fax: 816-767-3602