Pharmacokinetic interaction between nevirapine and rifampicin in HIV-infected patients with tuberculosis.
To determine whether rifampicin reduces serum concentrations of nevirapine and whether nevirapine modifies serum concentrations of rifampicin, levels of these agents were determined at steady state by high-performance liquid chromatography in 10 HIV-infected patients with tuberculosis. The median area under the curve (AUC) 0-12h of nevirapine before and after rifampicin was 56.2 and 32.8 microg/ml per hour, respectively ( p =.04). This represents a 31% reduction in serum nevirapine concentrations. The C(max) decreased from 5.6 to 4.5 microg/ml ( p =.04), which represented a 36% reduction. A 21% decrease in the C(min) was not statistically significant. Exposure to rifampicin did not significantly differ between those patients who were receiving and were not receiving nevirapine. However, our study shows that rifampicin reduces serum exposure to nevirapine. The clinical implications for this reduction remain to be established. Given that the lowest trough serum concentration of nevirapine exceeded by more than 40 times the protein binding adjusted median infective dose (IC(50)) of wild-type HIV in all patients, we suggest that there is no need to increase nevirapine dosage when it is given with rifampicin.
Ribera
E
E
Infectious Disease Service, Clinical Biochemistry Service, Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain. eribera@hg.vhebron.es
Pou
L
L
Lopez
R M
RM
Crespo
M
M
Falco
V
V
Ocaña
I
I
Ruiz
I
I
Pahissa
A
A
D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D000904:Antibiotics, Antitubercular / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D015658:HIV Infections / Q000150:complications / Q000378:metabolism*; D006801:Humans; D019829:Nevirapine / Q000097:blood / Q000493:pharmacokinetics*; D012293:Rifampin / Q000097:blood / Q000493:pharmacokinetics*; D014376:Tuberculosis / Q000150:complications / Q000378:metabolism*
D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D019829:Nevirapine; D012293:Rifampin