Pharmacokinetics of buspirone extended-release tablets: a single-dose study

The objective of this study is to evaluate the absorption of buspirone and its biotransformation to 1-(2-pyrimidinyl) piperazine (1-PP) from two different extended-release (ER) formulations of buspirone HCl tablets (12-hour and 24-hour in vitro release) and from a commercially available immediate-release (IR) tablet. A single dose of the 30 mg ER tablets was compared with two doses of the 15 mg IR tablet administered 12 hours apart. Eighteen healthy male subjects participated in this randomized, open-label, three-treatment crossover study. Blood samples were obtained at 22 time points from predose (0 hour) until 36 hours postdose, and plasma concentration of buspirone and 1-PP was determined by LC/tandem mass spectrometry method. The pharmacokinetic parameters AUC0-t, AUC0-infinity, Cmax, tmax, Ke, and t1/2 were calculated and statistically analyzed. The results indicated extended release of buspirone from the two test products in vivo with a 70% to 90% greater bioavailability in comparison with the IR formulation. The bioavailability of 1-PP from ER formulations appears to be equal to that from the IR formulation. Both buspirone ER tablets successfully delivered bioavailable buspirone with a reduction in peak drug and metabolite plasma levels, prolonged buspirone plasma concentrations, and decreased ratio of 1-PP to buspirone concentration with less intersubject variation when evaluated as a single-dose study in healthy human subjects.