title: Nonlinear kinetics and the 1-exp function in nephropharmacology.
abstract: The basic law in nephropharmacology states that pharmacokinetic parameters depend linearly on renal function. Few exceptions to linear dependence have been reported, e.g. substances with saturable tubular reabsorption or secretion. A further example is cyclosporin, which was found to be eliminated according to log-concave nonlinear kinetics in 3 patients with hepatotoxicity after kidney transplantation. The nonlinear cyclosporin kinetics were computer-fitted to the integrated forms of the 1-exp function and the Michaelis-Menten equation by nonlinear regression analysis. The same maximal velocity (Vmax = 23 ng ml-1 h-1) and Michaelis constant (Km = 686 ng ml-1) were calculated for cyclosporin when applying either the 1-exp function or the Michaelis-Menten equation. The nonlinear elimination of cyclosporin, however, was described even more closely by the 1-exp function than by the Michaelis-Menten equation.
authors: Abteilung für Allgemeine Innere Medizin und Nephrologie, Freie Universität Berlin, Klinikum Steglitz, Germany.
authors: F
authors: F
authors: Keller
authors: K
authors: K
authors: Erdmann
authors: M
authors: M
authors: Giehl
mesh_terms: D006801:Humans; D007668:Kidney / Q000502:physiology*; D007674:Kidney Diseases / Q000378:metabolism*; D010599:Pharmacokinetics