The Effect of Food on the Pharmacokinetics of Buspirone After Single Administration of a Sublingual Testosterone and Oral Buspirone Combination Tablet in Healthy Female Subjects

INTRODUCTION: A new combination tablet containing sublingual testosterone and oral buspirone (T+B) was developed to benefit a subgroup of women suffering from female sexual interest/arousal disorder, caused by dysfunctionally overactive sexual inhibition. AIM: The aim of this study was to compare the effect of food intake on the pharmacokinetics of buspirone, administered as a dual-route, dual-release combination tablet containing 0.5 mg testosterone (T) and 10 mg buspirone (B). METHODS: 19 healthy women took T+B under fed and fasted conditions during 2 overnight visits. The blood was sampled over a 24-hour period to determine the pharmacokinetics of buspirone and its active metabolite 1-(2-pyrimidinyl)piperazine (1-PP). Total testosterone levels were also assessed, at 5 time points and for quality control purposes only, as sublingual testosterone uptake is not expected to be influenced by prior food intake. MAIN OUTCOME MEASURE: PK profiles of buspirone and 1-PP. RESULTS: For buspirone, the 90% confidence intervals (CIs) of the observed fed/fasted ratios for the plasma area under the curve (AUC)(0-last), AUC(0-inf), and C(max) after administration of T+B were not contained within the prespecified bounds of 80% and 125%, except for the lower bound of AUC(0-inf). However, the 90% CIs of the observed fed/fasted ratios for the plasma AUC(0-last), AUC(0-inf), and C(max) of 1-PP were contained within the prespecified bounds, with the exception of the upper bound for C(max). The mean AUCs and C(max) for 1-PP did not differ between fed and fasted conditions. CONCLUSIONS: Administration of T+B after high-caloric food intake increased the bioavailability of buspirone but did not result in differences in T(max) when compared with fasted conditions. Both in fed and fasted conditions, T+B was generally well tolerated and safe. Exposure of 1-PP in fed and fasted conditions was comparable in both conditions. These results demonstrate that T+B can safely and effectively be used in both fed and fasted states. Gerritsen J, Bloemers J, van Rooij K, et al. The Effect of Food on the Pharmacokinetics of Buspirone After Single Administration of a Sublingual Testosterone and Oral Buspirone Combination Tablet in Healthy Female Subjects. J Sex Med 2020;8:186–194.