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Cyclosporine kinetics in renal transplantation
Author(s) -
Ptachcinski Richard J,
Venkataramanan Raman,
Rosenthal J Thomas,
Burckart Gilbert J,
Taylor Rodney J,
Hakala Thomas R
Publication year - 1985
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.1985.174
Subject(s) - bioavailability , pharmacokinetics , volume of distribution , dosing , medicine , urology , pharmacology , oral administration , transplantation , absorption (acoustics) , distribution (mathematics) , mathematical analysis , mathematics , physics , acoustics
The pharmacokinetics of cyclosporine were evaluated in 41 recipients of a cadaveric renal transplant. Cyclosporine was taken by mouth (mean dose 14 mg/kg) on one study day and was intravenously infused over 2 hours (mean dose 4.7 mg/kg) on the next study day. Cyclosporine was extracted from whole blood and analyzed by HPLC. After intravenous infusion, cyclosporine exhibited multicompartmental behavior. The mean (± SD) terminal disposition rate constant was 0.065 ± 0.036 hours −1 and the harmonic mean t ½ was 10.7 hours. The harmonic mean total body clearance of cyclosporine was 5.73 ml/min/kg and the mean apparent volume of distribution was 4.5 ± 3.6 L/kg. The absorption of oral cyclosporine was slow and incomplete. Peak blood cyclosporine concentrations (X̄ = 1,103 ng/ml) were reached between 1 and 8 hours after oral dosing (X̄ = 4 hours). The mean relative bioavailability was 27.6% ± 20%. Oral bioavailability was <10% in 17% of our subjects. The absorption and clearance of cyclosporine were highly variable. We conclude that the variability in the kinetics of cyclosporine makes trough blood level monitoring essential in the management of patients who receive renal transplants. Clinical Pharmacology and Therapeutics (1985) 38, 296–300; doi: 10.1038/clpt.1985.174