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Intravenous cyclosporine kinetics in renal failure
Author(s) -
Follath Ferenc,
K Markus Wen,
Vozeh Samuel,
Thiel Gilbert,
Brunner Felix,
Loertscher Rolf,
Lemaire Michel,
Nussbaumer Kurt,
Niederberger Werner,
Wood Alan
Publication year - 1983
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1983.226
Subject(s) - radioimmunoassay , volume of distribution , high performance liquid chromatography , chemistry , distribution (mathematics) , pharmacokinetics , renal function , whole blood , pharmacology , blood volume , kidney , endocrinology , medicine , chromatography , mathematical analysis , mathematics
Kinetics of the novel immunosuppressive cyclosporine were determined in four patients with terminal renal failure. After a short intravenous infusion (2.05 to 3.5 mg/kg in 4 hr), blood and plasma concentrations were measured (HPLC and radioimmunoassay [RIA]) up to 36 hr. After infusion, concentration curves of the drug were characterized by a rapid initial fall (t½α 0.10 ± 0.03 hr), followed by a biphasic elimination phase with corresponding t½s of 1.08 ± 0.25 hr (t½β) and 15.8 ± 8.4 hr (t½γ). The volumes of distribution, calculated from whole blood concentrations (HPLC), were 0.140 ± 0.48 l/kg (volume of the central compartment) and 3.49 ± 2.65 l/kg (volume of distribution at steady state), whereas systemic clearances were 0.369 ± 0.08 l/hr/kg. Blood levels measured by RIA exceeded the HPLC values after the fourth hour by up to 100%, indicating the production of cross‐reacting cyclosporine metabolites. Plasma concentrations were considerably lower than in whole blood. Elimination of unchanged cyclosporine in patients with renal failure appears to be of the same order as in those with normal kidney function. Modification of the initial dosage regimens is therefore probably not required. Clinical Pharmacology and Therapeutics (1983) 34, 638–643; doi: 10.1038/clpt.1983.226