Pharmacokinetic studies in volunteers with renal impairment

According to Luzius Dettli, drug clearance is a linear function of renal function. The slope of this function can be predicted from the fraction of a drug that is eliminated by the renal route. Pharmacokinetics in patients with functional anuria can, however, considerably deviate from these predictions. All basic pharmacokinetic parameters depend differently and specifically on renal function: drug clearance and distribution volume depend on creatinine clearance, but elimination half-life and plasma-binding correlate better with serum creatinine. For drugs with saturable tubular secretion, it can be shown that drug clearance depends on creatinine clearance in accordance with a left-bent, convex function, but not in accordance with a right-bent, concave function. It might be reasonable to postulate that the pharmacokinetics of every new approved drug should be determined in individuals with renal impairment. For drugs with no severe risks of adverse effects, these studies can be performed in volunteers with renal impairment better than in patients.