The clinical pharmacokinetics of rifampin and ethambutol in HIV-infected persons with tuberculosis

David C. Perlman, Yoninah Segal, Susan Rosenkranz, Petrie M. Rainey, Rory P. Remmel, Nadim Salomon, Richard Hafner, Charles A. Peloquin

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Abstract

Background. The pharmacokinetics of rifampin and ethambutol in HIV-infected patients with tuberculosis (TB) are incompletely characterized. We examined the pharmacokinetics of rifampin and ethambutol in a cohort of patients with HIV-related TB who were treated in the United States. Methods. Serum drug concentrations were determined 2, 6, and 10 h after dosing in 36 HIV-infected patients with TB who were taking rifampin and in 49 who were taking ethambutol. Observed serum concentrations were compared with published normal ranges and published data. Results. With daily dosing of rifampin (600 mg), 26 (77%) of 34 patients (95% confidence interval [CI], 59%-89%]) had a low maximum concentration of rifampin (<8 μg/mL), and 12 (35%; 95% CI, 20%-54%) had a very low maximum concentration (<4 μg/mL). With intermittent rifampin dosing (600 mg), 13 (68%) of 19 patients (95% CI, 44%-85%) had a low maximum concentration of rifampin, and 5 (26%; 95% CI, 11%-50%) had a very low maximum concentration. With daily ethambutol dosing (20 mg/kg), 33 (69%) of 48 patients (95% CI, 55%-81%) had a low maximum concentration of ethambutol (<2 μg/mL), and 18 (38%; 95% CI, 24%-53%) had a very low maximum concentration (<1 μg/mL). With intermittent ethambutol dosing (50 mg/kg twice weekly or 30 mg/kg thrice weekly), 13 (72%) of 18 patients (95% CI, 47%-88%) had a low maximum concentration of ethambutol (<4 μg/mL), and 5 (28%; 95% CI, 12%-54%]) had a very low maximum concentration (<2 μg/mL). Conclusions. In HIV-infected patients with TB who are receiving rifampin and ethambutol, low maximum concentrations of rifampin and ethambutol were common. For patients with HIV-related TB, therapeutic monitoring of rifampin and ethambutol levels may help clinicians achieve target serum concentrations.

Original languageEnglish (US)
Pages (from-to)1638-1647
Number of pages10
JournalClinical Infectious Diseases
Volume41
Issue number11
DOIs
StatePublished - Dec 1 2005

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Ethambutol
Rifampin
Tuberculosis
Pharmacokinetics
HIV
Confidence Intervals
Serum
Reference Values

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Perlman, D. C., Segal, Y., Rosenkranz, S., Rainey, P. M., Remmel, R. P., Salomon, N., ... Peloquin, C. A. (2005). The clinical pharmacokinetics of rifampin and ethambutol in HIV-infected persons with tuberculosis. Clinical Infectious Diseases, 41(11), 1638-1647. https://doi.org/10.1086/498024

The clinical pharmacokinetics of rifampin and ethambutol in HIV-infected persons with tuberculosis. / Perlman, David C.; Segal, Yoninah; Rosenkranz, Susan; Rainey, Petrie M.; Remmel, Rory P.; Salomon, Nadim; Hafner, Richard; Peloquin, Charles A.

In: Clinical Infectious Diseases, Vol. 41, No. 11, 01.12.2005, p. 1638-1647.

Research output: Contribution to journalArticle

Perlman, DC, Segal, Y, Rosenkranz, S, Rainey, PM, Remmel, RP, Salomon, N, Hafner, R & Peloquin, CA 2005, 'The clinical pharmacokinetics of rifampin and ethambutol in HIV-infected persons with tuberculosis', Clinical Infectious Diseases, vol. 41, no. 11, pp. 1638-1647. https://doi.org/10.1086/498024
Perlman, David C. ; Segal, Yoninah ; Rosenkranz, Susan ; Rainey, Petrie M. ; Remmel, Rory P. ; Salomon, Nadim ; Hafner, Richard ; Peloquin, Charles A. / The clinical pharmacokinetics of rifampin and ethambutol in HIV-infected persons with tuberculosis. In: Clinical Infectious Diseases. 2005 ; Vol. 41, No. 11. pp. 1638-1647.
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abstract = "Background. The pharmacokinetics of rifampin and ethambutol in HIV-infected patients with tuberculosis (TB) are incompletely characterized. We examined the pharmacokinetics of rifampin and ethambutol in a cohort of patients with HIV-related TB who were treated in the United States. Methods. Serum drug concentrations were determined 2, 6, and 10 h after dosing in 36 HIV-infected patients with TB who were taking rifampin and in 49 who were taking ethambutol. Observed serum concentrations were compared with published normal ranges and published data. Results. With daily dosing of rifampin (600 mg), 26 (77{\%}) of 34 patients (95{\%} confidence interval [CI], 59{\%}-89{\%}]) had a low maximum concentration of rifampin (<8 μg/mL), and 12 (35{\%}; 95{\%} CI, 20{\%}-54{\%}) had a very low maximum concentration (<4 μg/mL). With intermittent rifampin dosing (600 mg), 13 (68{\%}) of 19 patients (95{\%} CI, 44{\%}-85{\%}) had a low maximum concentration of rifampin, and 5 (26{\%}; 95{\%} CI, 11{\%}-50{\%}) had a very low maximum concentration. With daily ethambutol dosing (20 mg/kg), 33 (69{\%}) of 48 patients (95{\%} CI, 55{\%}-81{\%}) had a low maximum concentration of ethambutol (<2 μg/mL), and 18 (38{\%}; 95{\%} CI, 24{\%}-53{\%}) had a very low maximum concentration (<1 μg/mL). With intermittent ethambutol dosing (50 mg/kg twice weekly or 30 mg/kg thrice weekly), 13 (72{\%}) of 18 patients (95{\%} CI, 47{\%}-88{\%}) had a low maximum concentration of ethambutol (<4 μg/mL), and 5 (28{\%}; 95{\%} CI, 12{\%}-54{\%}]) had a very low maximum concentration (<2 μg/mL). Conclusions. In HIV-infected patients with TB who are receiving rifampin and ethambutol, low maximum concentrations of rifampin and ethambutol were common. For patients with HIV-related TB, therapeutic monitoring of rifampin and ethambutol levels may help clinicians achieve target serum concentrations.",
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AU - Segal, Yoninah

AU - Rosenkranz, Susan

AU - Rainey, Petrie M.

AU - Remmel, Rory P.

AU - Salomon, Nadim

AU - Hafner, Richard

AU - Peloquin, Charles A.

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N2 - Background. The pharmacokinetics of rifampin and ethambutol in HIV-infected patients with tuberculosis (TB) are incompletely characterized. We examined the pharmacokinetics of rifampin and ethambutol in a cohort of patients with HIV-related TB who were treated in the United States. Methods. Serum drug concentrations were determined 2, 6, and 10 h after dosing in 36 HIV-infected patients with TB who were taking rifampin and in 49 who were taking ethambutol. Observed serum concentrations were compared with published normal ranges and published data. Results. With daily dosing of rifampin (600 mg), 26 (77%) of 34 patients (95% confidence interval [CI], 59%-89%]) had a low maximum concentration of rifampin (<8 μg/mL), and 12 (35%; 95% CI, 20%-54%) had a very low maximum concentration (<4 μg/mL). With intermittent rifampin dosing (600 mg), 13 (68%) of 19 patients (95% CI, 44%-85%) had a low maximum concentration of rifampin, and 5 (26%; 95% CI, 11%-50%) had a very low maximum concentration. With daily ethambutol dosing (20 mg/kg), 33 (69%) of 48 patients (95% CI, 55%-81%) had a low maximum concentration of ethambutol (<2 μg/mL), and 18 (38%; 95% CI, 24%-53%) had a very low maximum concentration (<1 μg/mL). With intermittent ethambutol dosing (50 mg/kg twice weekly or 30 mg/kg thrice weekly), 13 (72%) of 18 patients (95% CI, 47%-88%) had a low maximum concentration of ethambutol (<4 μg/mL), and 5 (28%; 95% CI, 12%-54%]) had a very low maximum concentration (<2 μg/mL). Conclusions. In HIV-infected patients with TB who are receiving rifampin and ethambutol, low maximum concentrations of rifampin and ethambutol were common. For patients with HIV-related TB, therapeutic monitoring of rifampin and ethambutol levels may help clinicians achieve target serum concentrations.

AB - Background. The pharmacokinetics of rifampin and ethambutol in HIV-infected patients with tuberculosis (TB) are incompletely characterized. We examined the pharmacokinetics of rifampin and ethambutol in a cohort of patients with HIV-related TB who were treated in the United States. Methods. Serum drug concentrations were determined 2, 6, and 10 h after dosing in 36 HIV-infected patients with TB who were taking rifampin and in 49 who were taking ethambutol. Observed serum concentrations were compared with published normal ranges and published data. Results. With daily dosing of rifampin (600 mg), 26 (77%) of 34 patients (95% confidence interval [CI], 59%-89%]) had a low maximum concentration of rifampin (<8 μg/mL), and 12 (35%; 95% CI, 20%-54%) had a very low maximum concentration (<4 μg/mL). With intermittent rifampin dosing (600 mg), 13 (68%) of 19 patients (95% CI, 44%-85%) had a low maximum concentration of rifampin, and 5 (26%; 95% CI, 11%-50%) had a very low maximum concentration. With daily ethambutol dosing (20 mg/kg), 33 (69%) of 48 patients (95% CI, 55%-81%) had a low maximum concentration of ethambutol (<2 μg/mL), and 18 (38%; 95% CI, 24%-53%) had a very low maximum concentration (<1 μg/mL). With intermittent ethambutol dosing (50 mg/kg twice weekly or 30 mg/kg thrice weekly), 13 (72%) of 18 patients (95% CI, 47%-88%) had a low maximum concentration of ethambutol (<4 μg/mL), and 5 (28%; 95% CI, 12%-54%]) had a very low maximum concentration (<2 μg/mL). Conclusions. In HIV-infected patients with TB who are receiving rifampin and ethambutol, low maximum concentrations of rifampin and ethambutol were common. For patients with HIV-related TB, therapeutic monitoring of rifampin and ethambutol levels may help clinicians achieve target serum concentrations.

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