Re: Time-varing covariate

Dear Nick, In your reply to Siwei, you proposed the following code: > $PK > ; CL=(CLnon-renal*f(age) + CLrenal*f(renal_function)) * allometric WT > CL=(THETA(1)*EXP(THETA(2)*(AGE-40)) + THETA(3)*CLCR/100)*(WT/70)**0.75 I would like to make a comment on the coding of the renal function. If CLCR is expressed in ml/min, the expression THETA(3)*CLCR/100 represents the renal clearance of the individual with renal function CLCR, where THETA(3) is the drug's renal clearance for an individual with creatinine clearance of 100 ml/min (a reasonable value for an average individual but not a standard value). In my opinion, the allometric term should not be applied on this renal part of clearance. Therefore I suggest to use the following code line: ; CL= CLnon-renal*f(age)*allometric WT + CLrenal*f(renal_function) CL= THETA(1)*EXP(THETA(2)*(AGE-40))*(WT/70)**0.75 + THETA(3)*CLCR/100 If CLCR is expressed in ml/min/1.73m2 (the 'normalized renal function', often used in lab results, e.g. in the MDRD equation; useful for clinical judgement of renal function, but not for modeling or dosing purposes), your code could be used, but in that case I would prefer to first convert CLCR to ml/min (the 'true renal function') and then use the above code line. Note: Units of THETA(1) and THETA(3) are here in ml/min; for using the more conventional L/h, multiplication by 60/1000 should be added. best regards, Hans Proost Johannes H. Proost Dept. of Pharmacokinetics, Toxicology and Targeting University Centre for Pharmacy Antonius Deusinglaan 1 9713 AV Groningen, The Netherlands tel. 31-50 363 3292 fax 31-50 363 3247 Email: [email protected]