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From: <R.terHeine_at_radboudumc.nl>

Date: Tue, 5 Dec 2017 17:17:28 +0000

Dear all,

I am wondering what your thoughts are on the allometric scaling of clearance of renally extreted drugs, where we have estimations renal function.

Simply scaling the predicted glomerular filtration rate from, for example, the Cockroft-gault equation seems inappropriate, since weight is already a part of the equation. Standardizing this to weight in the Cockroft-gault equation can be done, a solution has been discussed here: http://cognigencorp.com/nonmem/current/2013-August/4697.html

However, in the recent years some new equations to calculate glomerular filtration rate from endogenous markers have emerged. For example the CKD-EPI CREATININE CYSTATIN C equation https://www.kidney.org/content/ckd-epi-creatinine-cystatin-equation-2012 . As the addition of a muscle mass independent endogenous marker like cystatin C is known to provide better estimations of GFR in, for example, cachectic patients, it is likely that this equation may outperform to predict renally filtrated compounds in this patient group. It is rather odd that this CKD-EPI equation does not contain any measure of body size. The outcome of this equation is a GFR scaled to a BSA of 1.73m^2.

I am wondering how you would allometrically scale the eGFRs from these CKD EPI equations to, for example, fat-free mass.

Cheers!

Rob

R. ter Heine, PhD, PharmD

Hospital Pharmacist-Clinical Pharmacologist

Radboudumc, Nijmegen, The Netherlands

Het Radboudumc staat geregistreerd bij de Kamer van Koophandel in het handelsregister onder nummer 41055629.

The Radboud university medical center is listed in the Commercial Register of the Chamber of Commerce under file number 41055629.

Received on Tue Dec 05 2017 - 12:17:28 EST

Date: Tue, 5 Dec 2017 17:17:28 +0000

Dear all,

I am wondering what your thoughts are on the allometric scaling of clearance of renally extreted drugs, where we have estimations renal function.

Simply scaling the predicted glomerular filtration rate from, for example, the Cockroft-gault equation seems inappropriate, since weight is already a part of the equation. Standardizing this to weight in the Cockroft-gault equation can be done, a solution has been discussed here: http://cognigencorp.com/nonmem/current/2013-August/4697.html

However, in the recent years some new equations to calculate glomerular filtration rate from endogenous markers have emerged. For example the CKD-EPI CREATININE CYSTATIN C equation https://www.kidney.org/content/ckd-epi-creatinine-cystatin-equation-2012 . As the addition of a muscle mass independent endogenous marker like cystatin C is known to provide better estimations of GFR in, for example, cachectic patients, it is likely that this equation may outperform to predict renally filtrated compounds in this patient group. It is rather odd that this CKD-EPI equation does not contain any measure of body size. The outcome of this equation is a GFR scaled to a BSA of 1.73m^2.

I am wondering how you would allometrically scale the eGFRs from these CKD EPI equations to, for example, fat-free mass.

Cheers!

Rob

R. ter Heine, PhD, PharmD

Hospital Pharmacist-Clinical Pharmacologist

Radboudumc, Nijmegen, The Netherlands

Het Radboudumc staat geregistreerd bij de Kamer van Koophandel in het handelsregister onder nummer 41055629.

The Radboud university medical center is listed in the Commercial Register of the Chamber of Commerce under file number 41055629.

Received on Tue Dec 05 2017 - 12:17:28 EST