Peppermint oil enhances cyclosporine oral bioavailability in rats: Comparison with D-α-tocopheryl poly(ethylene glycol 1000) succinate (TPGS) and ketoconazole
✍ Scribed by Vincent J. Wacher; Susan Wong; Harrison T. Wong
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 175 KB
- Volume
- 91
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
Peppermint oil inhibits cyclosporine metabolism in vitro. The current work compared the effects of peppermint oil, ketoconazole, and D-a-tocopheryl poly-(ethylene glycol 1000) succinate (TPGS) on cyclosporine oral bioavailability. Male Sprague-Dawley rats were administered cyclosporine (25 mg/kg) as the Sandimmune 1 formulation. Peppermint oil (100 mg/kg) tripled the mean cyclosporine maximum concentration (C max ) from 0.60 to 1.6 mg/mL and increased the area under the concentration versus time curve (AUC 0±I ) from 8.3 to 24.3 mgÁh/mL. The median time to reach C max (t max ) was increased from 2 to 6 h. Terminal half-life (10 h) and mean residence time (MRT; 15 h) were unaffected. Coadministration of TPGS (50 mg/kg) with cyclosporine in a saline vehicle doubled cyclosporine C max from 1.3 to 2.9 mg/mL and increased AUC 0±I from 28.5 to 59.7 mgÁh/mL. The t max was unchanged (3 h). Terminal half-life and MRT were increased by 44% (15.4 versus 10.7 h) and 24% (19.9 versus 16.0 h), respectively. Cyclosporine pharmacokinetics were not altered when corn oil was used instead of saline as a gavage vehicle, however the TPGS effect was abolished. Ketoconazole (10 and 20 mg/kg) had no effect on cyclosporine absorption. The lack of a signi®cant ketoconazole effect may re¯ect poor metabolism of cyclosporine in rat intestinal tissue and suggests that inhibition of cytochrome P450 3A is not the only means by which peppermint oil enhances cyclosporine oral bioavailability.