| Autor: |
Conte Jr., John E., Golden, Jeffrey A., Kipps, Juliana E., Lin, Emil T., Zurlinden, Elisabeth, Conte, John E |
| Předmět: |
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| Zdroj: |
Clinical Pharmacokinetics; 2004, Vol. 43 Issue 6, p395-404, 10p |
| Abstrakt: |
Objective: To compare the steady-state plasma and intrapulmonary concentrations of oral rifampicin (rifampin) in men and women with and without AIDS.Design: Prospective nonblinded pharmacokinetic study.Participants: Ten men with AIDS, ten men without AIDS, ten women with AIDS, and ten women without AIDS.Methods: Rifampicin 600 mg was administered orally once daily for 5 days to 40 adult volunteers. Blood was obtained 2 hours after the last dose and at the time of bronchoalveolar lavage (BAL) performed 4 hours after the last dose. Rifampicin was measured in plasma, epithelial lining fluid (ELF) and alveolar cells. Standardised BAL was performed without systemic sedation. The volume of ELF was calculated by the urea dilution method, and alveolar cells were recovered by a standardised centrifugation technique. The volume of alveolar cells was calculated from the cell count and differential performed on the BAL fluid. Rifampicin was measured by high-performance liquid chromatography.Results: Sex or AIDS status had no effect on plasma concentrations of rifampicin at 2 hours, 4 hours, or in ELF. Plasma concentrations (mean +/- SD) of rifampicin at 2 hours (9.15 +/- 5.4 mg/L) were not significantly different (p > 0.05) from those at 4 hours (9.10 +/- 5.6 mg/L) following the last dose. The ELF concentration was 2.0 +/- 1.6 mg/L with a range of 0-7.3 mg/L and the ELF/plasma ratio at 4 hours was 0.2 +/- 0.2. Rifampicin was not detectable in ELF in eight subjects (three with AIDS and five without AIDS) or in alveolar cells in three subjects without AIDS. There was no significant effect of AIDS on alveolar cell concentrations of rifampicin. Alveolar cell concentrations of rifampicin were significantly greater in women (13.9 +/- 6.7 mg/L) than in men (6.6 +/- 4.1 mg/L) [p = 0.0003]. Alveolar cell rifampicin concentrations were 78% greater in smoking women (17.8 +/- 7.0 mg/L) than in nonsmoking women (10.0 +/- 2.4 mg/L), but the difference was not significant (p > 0.05). CD4+ cell counts in the AIDS subjects were not correlated with the concentrations of rifampicin in plasma, ELF or alveolar cells.Conclusions: The absorption of oral rifampicin was not affected by sex or AIDS. Plasma and alveolar cell concentrations were not significantly different, were both greater than ELF concentrations, and were adequate to inhibit Mycobacterium tuberculosis. Considerable interpatient variability was detected despite witnessed drug administration. The clinical significance of these findings is unknown but merits further investigation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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