title: Cyclosporin pharmacokinetics in heart-lung transplant recipients with cystic fibrosis. Effects of pancreatic enzymes and ranitidine.
abstract: Cyclosporin (CsA) is currently the main immunosuppressive agent used in organ transplantation with considerable improvement in graft survival. Oral CsA solution is highly lipophilic, and its bioavailability may be reduced in cystic fibrosis (CF) heart-lung transplant recipients with pancreatic, gastrointestinal, and hepatic insufficiency. The bioavailability of oral CsA solution in 7 CF transplant recipients (5 male and 2 female with a mean age of 27 years and a mean weight of 49 kg) and 3 non-CF heart-lung recipients (1 male and 2 female with a mean age of 41 years and a mean weight of 60 kg) was studied. Following intravenous CsA administration, the kinetic curves were similar with no significant difference in the volume of distribution and clearance of CsA demonstrated between the CF and non-CF groups. The mean daily dose of oral CsA in 7 CF subjects (23.3 mg.kg-1) was significantly higher than the 3 non-CF heart-lung recipients (4.8 mg.kg-1). The mean maximum blood concentration of CsA for the oral dose was 776 ng.ml-1 for the 7 CF subjects, which was comparable with the mean peak values of 789 ng.ml-1 for the 3 non-CF control subjects. Poor enteral absorption of CsA probably accounts for the significantly lower mean bioavailability in the 7 CF subjects (14.9%) compared with the 3 non-CF control subjects (39.4%). The effects on the bioavailability of oral CsA solution by pancreatic enzymes (Creon) and histamine-2 antagonist (ranitidine) were also evaluated in the 7 CF subjects. No significant difference was demonstrated.
authors.affiliation: Department of Cardiac Surgery, Royal Brompton, National Heart and Lung Hospital, London, UK.
authors.forename: V T
authors.initials: VT
authors.lastname: Tsang
authors.forename: A
authors.initials: A
authors.lastname: Johnston
authors.forename: F
authors.initials: F
authors.lastname: Heritier
authors.forename: N
authors.initials: N
authors.lastname: Leaver
authors.forename: M E
authors.initials: ME
authors.lastname: Hodson
authors.forename: M
authors.initials: M
authors.lastname: Yacoub
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000601:surgery; D004347:Drug Interactions; D005260:Female; D016041:Heart-Lung Transplantation / Q000502:physiology*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D010194:Pancreatin / Q000494:pharmacology*; D011899:Ranitidine / Q000494:pharmacology*
chemical_list: D010194:Pancreatin; D016572:Cyclosporine; D011899:Ranitidine