Concordance of Direct and Indirect Measures of Medication Adherence in A Treatment Trial for Cannabis Dependence.

The current study compared adherence rates as measured by two indirect measurement methods (pill count and daily medication diary) to two direct measurement methods (urine riboflavin and serum 6-OH-buspirone level measurement) among participants (n = 109) in a medication treatment trial for cannabis dependence. Pill count and diary data showed high levels of percent agreement and strong kappa coefficients throughout the study. Riboflavin levels indicated lower level of percent in adherence during the study as compared to both pill count and self-report. In the subset of participants with 6-OH-buspirone levels (n = 58), the kappa coefficient also showed low to moderate agreement between the pill count and medication diaries with 6-OH-buspirone levels. In contrast to pill count and medication diaries, adherence as measured by riboflavin and 6-OH-buspirone significantly decreased over time. The findings from this study support previous work demonstrating that pill count and patient self-report of medication taking likely overestimate rates of medication adherence, and may become less reliable as the duration of a clinical trial increases.

The influences of aconitine, an active/toxic alkaloid from aconitum, on the oral pharmacokinetics of CYP3A probe drug buspirone in rats.

Aconitine (AC), an active/toxic alkaloid from Aconitum species, is commonly present in Traditional Chinese Medicine (TCM) prescriptions because of the great effectiveness of Aconitum for the treatment of rheumatoid arthritis, cardiovascular diseases, and tumors in clinic. Buspirone (BP) is a sensitive CYP3A probe drug that is administered through oral/intravenous routes as recommended by the U.S. Food and Drug Administration. This study aims to investigate the influences of AC (0.125 mg/kg, oral) on first-pass (intestinal and hepatic) CYP3A activity by using oral BP as the probe in rats. The pharmacokinetics of oral buspirone hydrochloride at different doses (12.5, 25, and 50 mg/kg) were conducted. The pharmacokinetics of oral BP in rats pretreated with single dose or multiple doses (7-day) of AC were investigated. The plasma concentrations of BP and its major metabolites [1-(2-pyrimidinyl)piperazine (1-PP) and 6'-hydroxybuspirone (6'-OH-BP)] were determined. The formation ratios of 1-PP and 6'-OH-BP from BP (AUC0-∞ of 1-PP/AUC0-∞ of BP and AUC0-∞ of 6'-OH-BP/AUC0-∞ of BP values) showed no alternation when the dose of BP changed. Single dose of AC decreased the AUC0-∞ of BP by 53% but increased the formation ratio of 6'-OH-BP by 74% (P<0.05). Multiple AC exposure increased the AUC0-∞ of BP by 110%, and the formation ratios of 1-PP and 6'-OH-BP from BP were increased by 229% and decreased by 95%, respectively (P<0.05). Conclusively, single/multiple AC exposure did not alter the first-pass CYP3A activity when using oral BP as probe in rats. Nevertheless, multiple AC exposure had markedly changed the production of BP metabolites.