Kees, Frieder and Bucher, Michael and Schweda, Frank and Gschaidmeier, Harald and Burhenne, Jürgen and Mikus, Gerd and Faerber, Lothar (2006) Comparative bioavailability of the microemulsion formulation of cyclosporine (Neoral) with a generic dispersion formulation (Cicloral) in young healthy male volunteers. THERAPEUTIC DRUG MONITORING, 28 (3). pp. 312-320. ISSN 0163-4356,
Full text not available from this repository. (Request a copy)Abstract
The aim of this study was to compare the bioavailability of cyclosporine (CyA) from the generic dispersion formulation Cicloral (CIC) with the microemulsion formulation Neoral (NEO) and the original Sandimmune (SIM) capsules after single doses of 100, 300, or 600 mg of drug, respectively. The study was performed according to an open 3-period crossover design with 12 young healthy male volunteers for each dosage. The concentrations of CyA and its main metabolites were determined by high performance liquid chromatography in whole blood and urine up to 48 hours postdosing. Peak concentrations and area under the time-concentration curve were greater for the NEO and CIC formulations compared with SIM, and the mean bioavailability of CIC was significantly (P < 0.05) lower compared with NEO. The bioavailability of SIM compared with NEO was 54% to 71%, in agreement with previous results. Bioequivalence was not demonstrated between CIC (test) and NEO (reference) as the 90% confidence intervals were outside the 80% to 125% guidelines based on log-transformed AUCs, and were 75.2% to 87.7% at 100mg, 79.2% to 91.8% at 300mg, and 76.6% to 94.5% at 600mg doses. The respective values for C-max were 78.9% to 94.6%, 80.7% to 95.0%, and 71.4% to 84.1%. A good correlation was demonstrated between the urinary recovery of CyA and the AUC(4). Therefore, the urinary recovery of CyA may be helpful as a surrogate parameter for the systemic exposure of patients to CyA. Whereas the relative amount of hydroxylated metabolites (AM I, AM9, AM1c) was similar for all formulations and doses, the urinary recovery of the N-demethylated metabolite AM4N decreased with increasing dose indicating saturable metabolism. No relationship could be demonstrated between CYP3A activity using dextromethorphan as a probe for the metabolic clearance of CyA.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IMMUNOSUPPRESSIVE DRUGS; TRANSPLANT PATIENTS; CYTOCHROME-P450 3A; PHARMACOKINETIC PROPERTIES; TROUGH LEVEL; DISPOSITION; PERFORMANCE; BIOEQUIVALENCE; ABSORPTION; PSORIASIS; cyclosporine metabolites; pharmacokinetics; bioequivalence; dextromethorphan; phenotyping |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Prof. Frieder Kees |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Feb 2021 10:07 |
| Last Modified: | 15 Feb 2021 10:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34522 |
Actions (login required)
 |
View Item |
