A STUDY OF PHARMACOKINETIC INTERACTION BETWEEN BUSPIRONE AND ALPRAZOLAM AT STEADY-STATE

The steady-state pharmacokinetic interaction between buspirone and alp razolam was evaluated in a parallel study with two groups of 12 male v olunteers each. On days 1 to 7, group I subjects received a 1-mg alpra zolam tablet every 8 hours (q8h) (TRT 1) and group 11 subjects receive d 2 X 5-mg buspirone tablets q8h (TRT 2). On days 8 through 14, all su bjects received a combination of 1-mg alprazolam and 2 x 5-mg buspiron e tablets q8h (TRT 3). Plasma samples, collected 0 to 8 hours after th e morning dose on days 7 and 14, were analyzed for buspirone, alprazol am and their metabolites, 1-PP, and alpha-HO-alprazolam, respectively. Additional samples were collected before the morning dose on days 5 a nd 6 of each session to monitor the attainment of steady state. Steady -state pharmacokinetic parameters Cmax, Tmax, AUC0-8, and Cmin were ca lculated. The results indicated that for alprazolam, there was a small (<10%) increase in Cmax and AUC when coadministered with buspirone. F or buspirone, there was a 10% and 29% increase in Cmax and AUC, when c oadministered with alprazolam. These values were within the normal var iability observed with this class of drugs. Except for a 14% decrease in Cmin for alpha-HO-alprazolam, coadministration of buspirone and alp razolam did not affect the parameters for the metabolites. The results of this study suggest that coadministration of buspirone and alprazol am did not markedly affect the steady-state pharmacokinetics of either drug.