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Serum Creatinine and Drug Half-Lives in Renal Failure

Donald Perrier, MS; Milo Gibaldi, PhD
JAMA. 1972;221(8):918. doi:10.1001/jama.1972.03200210062028.
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To the Editor.—  Serum creatinine concentrations as well as creatinine clearances have been used as a basis for adjusting the dosage regimen of certain drugs in patients with impaired renal function. Although mathematical relationships have been developed by Dettli et al1 relating the first-order elimination of a drug in renal failure to creatinine clearance, little has been done to relate the half-life or elimination rate of a drug to steady-state serum creatinine levels. Where serum creatinine has been employed to modify dosage regimens in patients with renal failure, it appears that the half-life of a drug was empirically assumed to be related directly to the steady-state serum creatinine concentration.2-4It can be demonstrated mathematically that creatinine clearance is inversely proportional to the steady-state serum creatinine concentration where the proportionality constant is the endogenous production rate of creatinine. The validity of this relationship can be illustrated by plotting creatinine


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