Abstract
On the basis of the reports that beta-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 less than 0.025), and this was associated with prolongation of tmax from 3.00 +/- 1.69 h to 4.33 +/- 1.51 h (P less than 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 less than 0.025). Our findings suggest that beta-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.
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More From: European journal of drug metabolism and pharmacokinetics
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