title: Cyclosporine-drug interactions and the influence of patient age.
abstract: Cyclosporine-drug interactions in adult transplant patients and the impact of age were studied. The medical records of transplant patients receiving cyclosporine therapy were identified. Data on patient demographics, cyclosporine dosages, dosage form, blood trough concentrations, clinical laboratory test values, and concurrent medications were collected. One-compartment models for oral and i.v. administration were used to fit cyclosporine concentration data to population pharmacokinetic and statistical models. Nonlinear mixed-effect modeling (NONMEM) software was used. The influence of covariates, including but not limited to concomitant medications and age, on cyclosporine pharmacokinetics was evaluated. The records of 100 patients (36 women and 64 men) were reviewed. A mean +/- S.D. of 9 +/- 2 and 9 +/- 1 medications per day were consumed by patients < 60 and > or = 60 years old, respectively. Mean population pharmacokinetic values of 0.407 L/hr/kg for clearance, 4.0 L/kg for volume of distribution, 31% for bioavailability, and 10.6 hours for half-life were determined on the basis of 569 blood cyclosporine levels. Twelve medications (sertraline, losartan, valsartan, quinine, atorvastatin, simvastatin, pravastatin, fluvastatin, alendronate, digoxin, acyclovir, and oxycodone) with previously unconfirmed pharmacokinetic interactions with cyclosporine were identified as interacting. There was no correlation between age and interactions. Patients taking cyclosporine were at risk for pharmacokinetic drug interactions when cyclosporine was used in combination with sertraline, losartan, valsartan, quinine, atorvastatin, simvastatin, pravastatin, fluvastatin, alendronate, digoxin, acyclovir, and oxycodone. Transplant patients 60-75 years of age had cyclosporine-drug interactions similar to those in younger patients.
authors.affiliation: University of Washington Medical Center, Seattle 98195-6015, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lill
authors.forename: L A
authors.initials: LA
authors.lastname: Bauer
authors.forename: J R
authors.initials: JR
authors.lastname: Horn
authors.forename: P D
authors.initials: PD
authors.lastname: Hansten
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D016001:Confidence Intervals; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D006084:Graft Rejection / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D012044:Regression Analysis; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A