Two- and four-day rifampin chemoprophylaxis regimens induce oxidative metabolism.

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RESUMO

The effects of two short-term chemoprophylaxis regimens of rifampin (2 or 4 days) on oxidative metabolism were investigated in 14 healthy subjects. Seven subjects received 600 mg of rifampin twice daily on study days 6 and 7 (group A), and seven subjects received 600 mg of rifampin once daily on days 4, 5, 6, and 7 (group B). Antipyrine (18 mg/kg of body weight) was administered orally on days 1, 8, and 15. Short-term rifampin regimens increased oral clearance of antipyrine in both groups compared with the baseline value (P less than 0.05), and group B displayed a larger percent increase over the baseline value than group A did (70.5 +/- 14.3 versus 33.1 +/- 18.1; P less than 0.05). The partial metabolic clearance (CLM) of antipyrine to 3-hydroxymethylantipyrine (HMA) on day 8 increased 71 and 108% for regimens A and B, respectively (P less than 0.05 for both). The corresponding increases in CLM to norantipyrine (NORA) were 57 and 98% (P less than 0.05 for both). CLM to 4-hydroxyantipyrine (OHA) on day 8 increased 64% for regimen A (P = 0.08) and 97% for regimen B (P less than 0.05) compared with the baseline. Although CLM to HMA and OHA on day 15 remained greater than 50% over the baseline with both regimens, CLM to NORA on day 15 was less than 25% over the baseline with both regimens. Thus, both short-term rifampin chemoprophylaxis regimens increased antipyrine clearance for at least 1 week. The increase tended to be higher with the 4-day regimen. The pattern observed for the CLMS suggests that more than one P-450 enzyme is affected.

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