Bioequivalence of 1 and 5 mg Tacrolimus Capsules Using a Replicate Study Design
| Autor: | Wayne A. Colburn, Qais Mekki, Dawna Dressler, Ihor Bekersky |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Diarrhea Male Knee Joint Cmax Capsules Pharmacology Bioequivalence Tacrolimus Dosage form Pharmacokinetics Oral administration Humans Medicine Pharmacology (medical) Purpura Kidney transplantation Cross-Over Studies Dose-Response Relationship Drug business.industry Headache medicine.disease Arthralgia Crossover study Abdominal Pain Therapeutic Equivalency Area Under Curve Female business Immunosuppressive Agents |
| Zdroj: | The Journal of Clinical Pharmacology. 39:1032-1037 |
| ISSN: | 0091-2700 |
| Popis: | Tacrolimus (FK506, Prograf) is marketed for the prophylaxis of organ rejection following allogenic liver or kidney transplantation. A previously conducted, randomized, 24-subject, crossover bioavailability study of 1 and 5 mg capsules (one period each) failed to demonstrate bioequivalence. A single-dose, four-period, four-sequence, randomized, crossover, replicate study (N = 32) was therefore used to evaluate the bioequivalence of the marketed 1 and 5 mg capsules in healthy volunteers. Tacrolimus blood concentrations were measured serially over 72 hours using a commercially available ELISA assay. Noncompartmental pharmacokinetic parameters were determined. Ninety percent CIs of log-transformed parameter ratios were 90.5-101.9, 87.1-101.7, and 89.7-103.8 for Cmax, AUC0-t, and AUC0-infinity, respectively. Since all values were within 80% to 125%, the capsules are bioequivalent. Based on %CVs, intersubject variability was approximately two to three times greater than intrasubject variability. The safety of single 5 mg oral tacrolimus doses administered to healthy volunteers at 7-day intervals was also ascertained. |
| Databáze: | OpenAIRE |
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