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• W2157798413 abstract "Cyclosporin A (CyA) tissue distribution kinetics was extensively studied after single 1.2-, 6-, and 30-mg/kg CyA doses (via 2-min i.v. infusion) to rats. Drug concentrations in blood and various tissues were measured using a specific radioimmunoassay. Based on total blood concentration data alone, CyA systemic pharmacokinetics appeared essentially linear. However, after taking the saturable, nonlinear blood cell binding into account, multiple nonlinear factors were identified. Intrinsic clearance at 30 mg/kg was about half the value at the two lower doses. Tissue distribution was also dose-dependent, with evidence of saturable binding in many tissues. In general, blood binding saturation (dissociation constant K(D) = 0. 18 microg/ml) occurred at a lower dose (concentration) than saturation of tissue binding (K(D), 0.005-0.77 microg/g), such that the volume of distribution at steady state first increased as the dose increased from 1.2 to 6 mg/kg, and then decreased as the dose increased to 30 mg/kg. Tissue binding was further investigated by various graphical analyses. Some organs showed a monophasic (single site) Scatchard plot of the tissue data at steady state, with high K(D) values. In other organs, biphasic binding characteristics were observed with the K(D) values of the high-affinity site in the same range as the K(D) reported for the binding of CyA with cyclophilin, the putative target. Saturable tissue binding may therefore influence not only the pharmacokinetics but also the efficacy of CyA." @default.
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• W2157798413 date "2000-05-01" @default.
• W2157798413 modified "2023-09-26" @default.
• W2157798413 title "Dose-dependent pharmacokinetics of cyclosporin A in rats: events in tissues." @default.
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