Bioequivalence evaluation of menthol after oral administration of peppermint oil soft capsules in dogs

Abstract

A randomized, two-way, crossover, bioequivalence study in 6 beagle dogs was conducted to compare the bioavailability of two peppermint oil formulations, soft capsule and hard capsule. The drug was given in a single dose of two capsules (total, 200 mg), and blood samples were withdrawn during the 12 h after drug administration. Menthol (CAS 2216-51-5) as the main component of peppermint oil was determined by a gas chromatography-tandem mass spectrometry (GC-MS/MS) method after cleavage with p-glucuronidase. The following pharmacokinetic variables were computed for the two formulations: maximum concentration (C_max), time to maximum concentration (T_max), half-life of elimination (t_1/2), mean residence time (MRT), and areas under the plasma concentration-time curve (AUC_0–t and AUC_0–∞). For calculation of the 90% confidence interval (CI), an analysis of variance (ANOVA) was carried out.

The results indicated that treatment and subject had statistically significant effect on AUC_0–t, AUC_0–∞ and C_max, and the 90% CIs for AUC_0–t, AUC_0–∞ and C_max were outside the acceptable bioequivalence range. The relative bioavailability was 121.4 ± 10.6% for AUC_0–∞. Therefore, it can be concluded that the two formulations are not bioequivalent and the bioavailability of soft capsules is significantly higher than that of hard capsules.

Key words

Beagle dogs - CAS 2216-51-5 - Menthol - Peppermint oil, bioequivalence, pharmacokinetics, soft or hard capsule

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