Bioequivalence evaluation of menthol after oral administration of peppermint oil soft capsules in dogs.
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 The drug was given in a single dose of two capsules (total, 200 mg), and blood samples were withdrawn during the 12 h after drug administration.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/I MS) method after cleavage with beta-glucuronidase. The following pharmacokinetic variables were computed for the two formulations: maximum concentration (Cmax), time to maximum concentration (Tmax), half-life of elimination (t1/2), mean residence time (MRT), and areas under the plasma concentration-time curve (AUC(0-t) and AUC(0-infinity)). 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-infinity), and Cmax, and the 90% CIs for AUC(0-t), AUC(0-infinity), and Cmax were outside the acceptable bioequivalence range. The relative bioavailability was 121.4 +/- 10.6% for AUC(0-infinity). 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.
Wu
Jing-Fang
JF
Center for Instrumental Analysis, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, P. R. China.
Xiang
Bing-Ren
BR
Li
Kui-Xing
KX
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005966:Glucuronidase / Q000378:metabolism; D006207:Half-Life; D008297:Male; D013058:Mass Spectrometry; D036142:Mentha piperita; D008610:Menthol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D010938:Plant Oils / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D013810:Therapeutic Equivalency
D002214:Capsules; D010938:Plant Oils; D008610:Menthol; C015424:peppermint oil; D005966:Glucuronidase