Is it appropriate regarding patient preference to take Myrtol standardized enteric-coated soft capsules after a meal rather than at fasted state? A food–drug pharmacokinetic interaction study in healthy Chinese volunteers

Ting-Ting Zhao,1 Ling-Ling Zhu,2 Meng Chen,1 Quan Zhou1 1Department of Pharmacy, 2VIP Care Ward, Division of Nursing, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China Background: According to prescribing information for Myrtol standardized enteric-coated soft capsules, the medicine should be taken on an empty stomach. Some patients may experience stomach discomfort after oral administration in fasted state and would prefer to take the medicine after a meal. However, there is no literature addressing the effect of meal on absorption of this drug; therefore, it is desirable to explore the feasibility of taking the capsule after a meal from pharmacokinetic perspective.Methods: A gas chromatography coupled with triple quadruples mass spectrometry assay was established and validated for determining plasma concentrations of eucalyptol, a target component of Myrtol standardized capsules. A self-control clinical study was carried out in healthy male volunteers in fasted and fed states after a single oral dose of 300 mg capsules. Comparison of pharmacokinetic parameters in the two phases and bioequivalence evaluation were performed.Results: The specificity, sensitivity, accuracy, and precision of the assay satisfied the requirements for biopharmaceutical analysis. Pharmacokinetic parameters of eucalyptol (fasted vs fed) were as follows: maximal plasma concentrations (Cmax) (167.60±114.69 vs 518.89±314.47 ng·mL-1), time of maximum concentration (Tmax) (3.7±1.1 vs 4.8±0.7 h), elimination half-life (T1/2) (3.2±1.4 vs 2.6±0.7 h), area under the plasma concentration–time curve (AUC0–t) (584.91±369.90 vs 1,271.61±605.82 ng·h·mL-1), and AUC0–∞ (690.36±467.26 vs 1,458.02±720.21 ng·h·mL-1). There was statistically significant difference in Cmax, AUC0–t, and AUC0–∞ between the two dosing methods (P