The clinical pharmacokinetics of rifampin and ethambutol in HIV-infected persons with tuberculosis.
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 microg/mL), and 12 (35%; 95% CI, 20%-54%) had a very low maximum concentration (<4 microg/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 microg/mL), and 18 (38%; 95% CI, 24%-53%) had a very low maximum concentration (<1 microg/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 microg/mL), and 5 (28%; 95% CI, 12%-54%]) had a very low maximum concentration (<2 microg/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.
Perlman
David C
DC
Beth Israel Medical Center, New York, NY 10003, USA. dperlman@bethisraelny.org
Segal
Yoninah
Y
Rosenkranz
Susan
S
Rainey
Petrie M
PM
Remmel
Rory P
RP
Salomon
Nadim
N
Hafner
Richard
R
Peloquin
Charles A
CA
D000328:Adult; D000995:Antitubercular Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D012293:Rifampin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000188:drug therapy*
D000995:Antitubercular Agents; D004977:Ethambutol; D012293:Rifampin