title: Differences in bioavailability between oral cyclosporine formulations in maintenance renal transplant patients.
abstract: Previous studies of healthy volunteers and small numbers of transplant recipients have suggested that the oral solution formulation of Sandimmune (cyclosporine [CsA]; Sandoz Pharmaceuticals, East Hanover, NJ) is bioequivalent to the soft gelatin capsule (SGC) formulation. However, there is conflicting evidence as to whether the two formulations are bioequivalent in all patients; to date, there are no published studies that explicitly address their bioequivalence in patients. We conducted a randomized, open-label, two-sequence, two-period, crossover study. Of 20 maintenance renal transplant recipients shown by a screening pharmacokinetic (PK) profile to be poor absorbers of CsA, half were randomized to receive first the SGC formulation and half the oral solution formulation for a period of 7 days. Each patient then underwent a 12-hour PK profile on the last day of the assigned formulation before a crossover to receive the other formulation and repeat the 7-day treatment and PK profile cycle. The results showed that peak and total exposure to CsA was greater with the SGC formulation. The SGC-oral solution ratios indicated an average 38% greater peak and 11% greater total exposure for the SGC formulation (P < 0.01 and P = 0.09, respectively). Trough levels were more similar between formulations, with SGC showing an average of 5% greater troughs (P > 0.10). In our selected population of malabsorbers, the SGC formulation made a difference in drug exposure.
authors.affiliation: Department of Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL 35294-0006, USA. john_curtis@nrtc.dom.uab.edu
authors.forename: J J
authors.initials: JJ
authors.lastname: Curtis
authors.forename: R
authors.initials: R
authors.lastname: Barbeito
authors.forename: J
authors.initials: J
authors.lastname: Pirsch
authors.forename: R M
authors.initials: RM
authors.lastname: Lewis
authors.forename: D H
authors.initials: DH
authors.lastname: Van Buren
authors.forename: S
authors.initials: S
authors.lastname: Choudhury
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004304:Dosage Forms; D016903:Drug Monitoring; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D013810:Therapeutic Equivalency
chemical_list: D004304:Dosage Forms; D007166:Immunosuppressive Agents; D016572:Cyclosporine