• T L Putt, Stephen B Duffull, J B W Schollum, and R J Walker.
• Department of Medicine, University of Otago, Dunedin, New Zealand.
• Eur. J. Clin. Pharmacol. 2014 Oct 1;70(10):1221-6.

PurposeDose modification in renal impairment has traditionally been based on changes in estimated glomerular filtration rate (eGFR; estimated by creatinine clearance). However, many drugs are eliminated by tubular anionic and cationic transport where changes in eGFR may not necessarily reflect changes in tubular function. This study investigated the relationship between GFR and renal tubular function with reference to drug handling by using accepted drug probes.MethodsThree drug probes, (51)Cr-EDTA, fluconazole, and pindolol, were administered to patients who had varying degrees of renal impairment. Blood sampling, assays, and a pharmacokinetic analysis were performed for all drug probes and endogenous urate. Measured GFR ((51)Cr-EDTA clearance; mGFR) was compared to tubular anionic transport (urate clearance), tubular reabsorption (fluconazole clearance), and tubular cationic transport (S-pindolol clearance).ResultsA moderately strong association was demonstrated between the measured isotopic GFR and creatinine clearance (R(2) = 0.78). A moderate positive correlation was found between mGFR and proximal tubular anion transport and reabsorption (R(2) = 0.40-0.44, p < 0.0001). In contrast, cationic secretion correlated poorly with mGFR (R(2) = 0.11, p = 0.036).ConclusionsGiven that drug dosing schedules utilise eGFR values as the basis for modifying drug dosing, our results would suggest that a recommendation of a dose reduction according to eGFR alone should be treated with caution.

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