title: Cyclosporine pharmacokinetics in liver transplant recipients: evaluation of results using both polyclonal radioimmunoassay and liquid chromatographic analysis.
abstract: Pharmacokinetic variables were derived from cyclosporine measurements using liquid chromatography (HPLC) and radioimmunoassay with a non-selective polyclonal antibody (PARIA) in 11 orthotopic liver transplant recipients studied in paired oral and intravenous studies both before and after permanent clamping of the biliary T-tube. After oral drug administration, mean areas under blood cyclosporine concentration versus time curves before clamping were around 5.2-fold greater by PARIA than HPLC but 2.9-fold greater after clamping and closer to comparable values after intravenous cyclosporine (2.5 and 2.3-fold, respectively). Cyclosporine clearance was smaller by PARIA than HPLC (mean 7.3 versus 3.3 ml.min-1.kg-1, respectively, before clamping). Both values decreased by 25% after clamping (to 5.5 and 2.4 ml.min-1.kg-1, respectively), although there was no significant change in distribution or elimination half-lives (around 0.5 and 8 h, respectively). The mean bioavailability of oral cyclosporine increased significantly after clamping in 9 patients (from 10.6% to 28.1% by HPLC and from 14.8 to 35.1% by PARIA) but in two patients who developed the vanishing bile duct syndrome values fell to less than 10% and the proportional overestimation of cyclosporine concentrations by PARIA increased. Clamping had no singificant effect on the mean apparent volumes of distribution but values of Vz were approximately twice those of Vss (around 2.6 and 1.31.kg-1 by PARIA and HPLC respectively). Mean half lives after clamping were shorter following oral than intravenous cyclosporine (t 1/2 lambda 2 around 15 h enterally versus 8 h parenterally).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, England.
authors.forename: J M
authors.initials: JM
authors.lastname: Tredger
authors.forename: J
authors.initials: J
authors.lastname: Grevel
authors.forename: N
authors.initials: N
authors.lastname: Naoumov
authors.forename: C M
authors.initials: CM
authors.lastname: Steward
authors.forename: A A
authors.initials: AA
authors.lastname: Niven
authors.forename: B
authors.initials: B
authors.lastname: Whiting
authors.forename: R
authors.initials: R
authors.lastname: Williams
mesh_terms: D000284:Administration, Oral; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003524:Cyclosporins / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D016031:Liver Transplantation; D008297:Male; D011863:Radioimmunoassay
chemical_list: D003524:Cyclosporins