Does the intact nephron hypothesis provide a reasonable model for metformin dosing in chronic kidney disease?

This research explored the intact nephron hypothesis (INH) as a model for metformin dosing in patients with chronic kidney disease (CKD). The INH assumes that glomerular filtration rate (GFR) will account for all kidney drug handling even for drugs eliminated by tubular secretion like metformin. We...

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Bibliographic Details
Published inBritish journal of clinical pharmacology Vol. 87; no. 12; pp. 4868 - 4876
Main Authors Pradhan, Sudeep, Duffull, Stephen B., Wilson, Luke C., Kuan, Isabelle H. S., Walker, Robert J., Putt, Tracey L., Schollum, John B. W., Wright, Daniel F. B.
Format Journal Article
LanguageEnglish
Published England 01.12.2021
Subjects
chronic kidney disease
Creatinine
Glomerular Filtration Rate
Humans
intact nephron hypothesis
Kidney
Kidney Function Tests
Metformin
Nephrons
NONMEM
pharmacokinetics
Renal Insufficiency, Chronic - drug therapy
pharmacokinetics
metformin
chronic kidney disease
intact nephron hypothesis
NONMEM
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Summary:This research explored the intact nephron hypothesis (INH) as a model for metformin dosing in patients with chronic kidney disease (CKD). The INH assumes that glomerular filtration rate (GFR) will account for all kidney drug handling even for drugs eliminated by tubular secretion like metformin. We conducted two studies: (1) a regression analysis to explore the relationship between metformin clearance and eGFR metrics, and (2) a joint population pharmacokinetic analysis to test the relationship between metformin renal clearance and gentamicin clearance. The relationship between metformin renal clearance and eGFR metrics and gentamicin clearance was found to be linear, suggesting that a proportional dose reduction based on GFR in patients with CKD is reasonable.
Bibliography:Funding information
Healthcare Otago Charitable Trust; University of Otago Research Grant, Grant/Award Number: UORG, 109425; Auckland University of Technology; University of Otago Doctoral Scholarship; University of Otago Special Health Research Scholarship
The authors confirm that the Principal Investigator for this paper is Dr Daniel Wright.
Principal investigator
ISSN:0306-5251
1365-2125
DOI:10.1111/bcp.14919