Effects of salbutamol on the absorption and disposition of sulphamethoxazole in adult volunteers.

On the basis of the reports that β-adrenergic stimulation affects gastrointestinal motility in man as well as induces N-acetyltransferase in rat pineal gland, we decided to assess the effects of salbutamol pretreatment on the absorption as well as disposition of sulphamethoxazole (SMZ). After a control pharmacokinetic study of SMZ, each of six healthy volunteers took salbutamol at a dose of 4 mg four times daily for two weeks, and the kinetic study of SMZ was repeated after the morning dose on the fifteenth day. None of SMZ half-life, volume of distribution, renal and hepatic clearance rates was significantly altered. However, salbutamol pretreatment resulted in significant reduction in the absorption rate constant of SMZ from 1.168±0.509 h−1 (mean±S.D.) to 0.688±0.348 h−1 (P < 0.025), and this was associated with prolongation of tmax from 3.00±1.69 h to 4.33±1.51h (P < 0.025). Cmax, however, was not correspondingly reduced probably as a result of significant increase in the extent of SMZ absorption from 611±108 mg to 749±78 mg (P < 0.025). Our findings suggest that β-adrenergic stimulation does not significantly induce human hepatic N-acetyltransferase enzyme. However, it does reduce the absorption rate as well as increase the extent of absorption of SMZ.