how to obtain steady-state individual PK parameters in NONMEM

Dear NONMEM users, I have a one-compartment model with first order absorption with ADVAN2 TRANS2. Is there an easy way to obtain steady-state individual PK parameters (e.g., Cmax, Cmin, AUCtau) in NONMEM based on the posthoc estimates? Alternately, is there a way to simulate the steady-state concentration-time profiles NONMEM based on the posthoc estimates? Thank you for your input in advance. Juli

Dear Juli, Below are analytical solutions to Cmax, Tmax, Cmin and AUCtau for a one-compartment model with first order absorption. Write the solutions in $PK and output the calculated parameters in a table. If your posthoc parameter estimates are based on sparse data I would advice you to look into what magnitude of shrinkage these estimates are suffering from (See: Karlsson MO, Savic RM. Diagnosing model diagnostics. Clin Pharmacol Ther. 2007 Jul;82(1):17-20.). If the posthoc parameter estimates are heavily shrunk the same will go for your secondary calculated PK parameters. If you want to simulate steady state profiles the easiest way is to use a data-set with the SS data item (Steady State dose) and II data item (Inter dose Interval = TAU). See the NONMEM manual for further details on the use of these data items. ; ------------------------------------------------------------------------ Cmax,ss = (F * DOSE)/V*(1/(1-EXP(-KE)))*((KA*(1-EXP(-KE*TAU)))/(KE*(1-EXP(-KA*TAU))))**(KE/ (KE-KA)) Tmax,ss = (1/(KA-KE))*LN((KA*(1-EXP(-KE*TAU)))/(KE*(1-EXP(-KA*TAU)))) Cmin,ss = (F * DOSE)/V*(KA/(KA-KE))*((EXP(-KE*TAU)/(1-EXP(-KE*TAU)))-(EXP(-KA*TAU)/(1-EXP(- KA*TAU)))) (Or insert dummy data point into the data set (EVID=2)) AUCtau = F*DOSE/CL = F*DOSE/KE*V (Assumes regular dosing schedule and fix dose during treatment. In other cases an integration approach is necessary.) ; ------------------------------------------------------------------------ F = bioavailability (NONMEM code F1, if only oral data is used F1 is assumed to be 1 and apparent oral V and CL are estimated) TAU = Inter dosing interval KA = Absorption rate constant KE = Elimination rate constant (CL/V) V = Distribution volume In the code above I have written LN() to represent the natural logarithm of an expression. In NONMEM this should written LOG(). ** is used both here and in NONMEM to code for raised to the power of. ; ------------------------------------------------------------------------ Good luck! Kind regards, Martin Bergstrand, MSc, PhD student ----------------------------------------------- Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, Uppsala University ----------------------------------------------- P.O. Box 591 SE-751 24 Uppsala Sweden ----------------------------------------------- [EMAIL PROTECTED] ----------------------------------------------- Work: +46 18 471 4639 Mobile: +46 709 994 396 Fax: +46 18 471 4003