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

S. M. Borcherding, T. L. Bastian, Timothy Self, N. Abou-Shala, B. W. LeDuc, R. L. Lalonde

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Abstract

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 < 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 < 0.05). The partial metabolic clearance (CL(M)) of antipyrine to 3- hydroxymethylantipyrine (HMA) on day 8 increased 71 and 108% for regimens A and B, respectively (P < 0.05 for both). The corresponding increases in CL(M) to norantipyrine (NORA) were 57 and 98% (P < 0.05 for both). CL(M) to 4- hydroxyantipyrine (OHA) on day 8 increased 64% for regimen A (P = 0.08) and 97% for regimen B (P < 0.05) compared with the baseline. Although CL(M) to HMA and OHA on day 15 remained >50% over the baseline with both regimens, CL(M) to NORA on day 15 was <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 CL(M)s suggests that more than one P-450 enzyme is affected.

Original languageEnglish (US)
Pages (from-to)1553-1558
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume36
Issue number7
DOIs
StatePublished - Jan 1 1992

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Chemoprevention
Rifampin
Antipyrine
Cytochrome P-450 Enzyme System
Healthy Volunteers
Body Weight

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Borcherding, S. M., Bastian, T. L., Self, T., Abou-Shala, N., LeDuc, B. W., & Lalonde, R. L. (1992). Two- and four-day rifampin chemoprophylaxis regimens induce oxidative metabolism. Antimicrobial Agents and Chemotherapy, 36(7), 1553-1558. https://doi.org/10.1128/AAC.36.7.1553

Two- and four-day rifampin chemoprophylaxis regimens induce oxidative metabolism. / Borcherding, S. M.; Bastian, T. L.; Self, Timothy; Abou-Shala, N.; LeDuc, B. W.; Lalonde, R. L.

In: Antimicrobial Agents and Chemotherapy, Vol. 36, No. 7, 01.01.1992, p. 1553-1558.

Research output: Contribution to journalArticle

Borcherding, SM, Bastian, TL, Self, T, Abou-Shala, N, LeDuc, BW & Lalonde, RL 1992, 'Two- and four-day rifampin chemoprophylaxis regimens induce oxidative metabolism', Antimicrobial Agents and Chemotherapy, vol. 36, no. 7, pp. 1553-1558. https://doi.org/10.1128/AAC.36.7.1553
Borcherding SM, Bastian TL, Self T, Abou-Shala N, LeDuc BW, Lalonde RL. Two- and four-day rifampin chemoprophylaxis regimens induce oxidative metabolism. Antimicrobial Agents and Chemotherapy. 1992 Jan 1;36(7):1553-1558. https://doi.org/10.1128/AAC.36.7.1553
Borcherding, S. M. ; Bastian, T. L. ; Self, Timothy ; Abou-Shala, N. ; LeDuc, B. W. ; Lalonde, R. L. / Two- and four-day rifampin chemoprophylaxis regimens induce oxidative metabolism. In: Antimicrobial Agents and Chemotherapy. 1992 ; Vol. 36, No. 7. pp. 1553-1558.
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abstract = "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 < 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 < 0.05). The partial metabolic clearance (CL(M)) of antipyrine to 3- hydroxymethylantipyrine (HMA) on day 8 increased 71 and 108{\%} for regimens A and B, respectively (P < 0.05 for both). The corresponding increases in CL(M) to norantipyrine (NORA) were 57 and 98{\%} (P < 0.05 for both). CL(M) to 4- hydroxyantipyrine (OHA) on day 8 increased 64{\%} for regimen A (P = 0.08) and 97{\%} for regimen B (P < 0.05) compared with the baseline. Although CL(M) to HMA and OHA on day 15 remained >50{\%} over the baseline with both regimens, CL(M) to NORA on day 15 was <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 CL(M)s suggests that more than one P-450 enzyme is affected.",
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