PK-PD using 2 step approach

From MAJ_MARK_MARINO@wrsmtp-ccmail.army.mil Fri Jul 12 14:43:55 1996 Subject: PK-PD using 2 step approach Dear NONMEM users, I am working on a PK-PD model with a two step approach. First the PK is being done in adv4tr4. The parameters of clearance and volume are modeled as being dependent on weight and gender. I then take the results of the Bayesein PK parameters and feed them into the PD model to generate effect site amounts and effect using adv5tr1 fixing K1e to .001*K10. Since adv5tr1 uses amounts my EConc50 is truly an EAmount50. To back calculate a plasma EC50 I use the equation K1e * A1 = Keo * Ae and since K1e = .001*K10 .001 * K10 * C * Vc = Keo * Ae .001 * (CL / Vc) * C * Vc = Keo * Ae EC50 = Keo * Ae / (.001 * CL) My CL is dependent on both weight and gender giving me a EC50 that is dependent on weight and gender? Is this correct or is there something wrong with the way I am calculating my EC50? Any help would be appreciated. Mark T. Marino WRAIR