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Scand J Gastroenterol. 1992 Nov;27(11):961-7.

Cyclosporin pharmacokinetics after intravenous and oral administration in patients with Crohn's disease.

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  • 1Dept. of Internal Medicine and Gastroenterology C, Herlev University Hospital, Herlev, Copenhagen, Denmark.

Abstract

Cyclosporin kinetics were estimated after single-dose intravenous and oral administration in 12 patients with Crohn's disease in accordance with a three-compartment model with zero-order inputs. Cyclosporin was measured in whole blood with a specific monoclonal radioimmunoassay. The median bioavailability (f) was 23.7% (range, 0-49.1%); the distribution volume at steady state, 2.3 l/kg (range, 1.0-3.5 l/kg); clearance (CL), 7.6 ml/min/kg (range, 4.8-10.8 ml/min/kg); and t1/2(z) 7.9 h (range, 3.2-13.9 h). Both the extent and rate of bioavailability were significantly lower in six of the patients, who had low or undetectable cyclosporin levels during a preceding therapeutic trial. After repeated oral administration significant correlations were found between the single-dose f/CL ratios and the steady-state blood concentrations, indicating that the kinetics did not change markedly with time. We conclude that the disposition kinetics of cyclosporin in patients with Crohn's disease are comparable to those of other groups, whereas the bioavailability may be decreased. It is suggested that cyclosporin levels should be monitored closely, and intravenous treatment should be considered in patients with a rapid gut transit time, because cyclosporin absorption seems to follow zero-order kinetics.

PMID:
1455195
[PubMed - indexed for MEDLINE]
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