Nevirapine plasma concentrations and concomitant use of rifampin in patients coinfected with HIV-1 and tuberculosis.
OBJECTIVE
In countries with high numbers of HIV/tuberculosis coinfection nevirapine and rifampin are used extensively. However, limited data are available about whether or not nevirapine and rifampin can be safely coadministered without the plasma concentration of nevirapine falling below therapeutic levels.


METHODS
Blood samples for determination of nevirapine plasma concentrations were collected from patients using nevirapine 200 mg twice daily with or without concomitant rifampin. Bivariate and multivariate linear regression models were used to investigate factors possibly related to nevirapine concentrations.


RESULTS
We received 74 blood samples from patients using nevirapine plus rifampin, and collected blood samples from an equal number of controls using nevirapine only. Groups were similar for age, gender, weight, height and body mass index (BMI). In the rifampin group the mean nevirapine concentration was 5.47 +/- 2.66 mg/l, whereas in the control group the mean nevirapine concentration was 8.72 +/- 3.98 mg/l. In the rifampin group seven nevirapine trough concentrations were low (< 3.1 mg/l), while in the control group two patients had low nevirapine trough concentrations (P = 0.164). In the multivariate linear regression analysis, corrected for time after drug intake, the use of rifampin was significantly (P < 0.001) associated with lower nevirapine plasma concentrations, whereas higher BMI reached borderline significance (P = 0.065).


CONCLUSIONS
Although nevirapine plasma concentrations were 3.3 mg/l lower when co-administered with rifampin, still more than 86% of these patients had nevirapine plasma concentrations > 3.1 mg/l. Our results suggest that from a pharmacological point of view the majority of Thai coinfected patients, who have low BMIs, reach nevirapine plasma concentrations that are adequate for treatment of HIV. However this can only be undertaken if nevirapine plasma concentration monitoring is available and can be closely followed.
Autar
Reshma S
RS
The HIV-Netherlands Australia Thailand Research Collaboration, Thai Red Cross Aids Research Center, Bangkok, Thailand. saskia@hivnat.com
Wit
Ferdinand W N M
FW
Sankote
Jongkol
J
Mahanontharit
Apicha
A
Anekthananon
Thanomsak
T
Mootsikapun
Piroon
P
Sujaikaew
Khanjtta
K
Cooper
David A
DA
Lange
Joep M A
JM
Phanuphak
Praphan
P
Ruxrungtham
Kiat
K
Burger
David M
DM
D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019829:Nevirapine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D013785:Thailand; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy*
D000890:Anti-Infective Agents; D000904:Antibiotics, Antitubercular; D019829:Nevirapine; D012293:Rifampin