From: J.H. Proost <*j.h.proost*>

Date: Mon, 26 Aug 2013 16:09:55 +0200

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: j.h.proost

Received on Mon Aug 26 2013 - 10:09:55 EDT

Date: Mon, 26 Aug 2013 16:09:55 +0200

Dear Nick,

In your reply to Siwei, you proposed the following code:

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: j.h.proost

Received on Mon Aug 26 2013 - 10:09:55 EDT