8th Conference on Retroviruses and Opportunistic Infections


Chicago, IL - February 4 - 8, 2001



Pharmacokinetic interactions between rifampin and efavirenz in patients with tuberculosis and HIV infection

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:52 (abstract no. 32)

L. F. Lopez-Cortes1, R. Ruiz1, P. Viciana1, A. Alarcon1, E. Leon2, M. Sarasa3, Y. Lopez-Pua3, J. Gomez2, and J. Pachon1
1Hosp. Virgen del Rocío, Sevilla; 2Hosp. Valme, Sevilla; and 3Hosp. Clin., Barcelona, Spain.

BACKGROUND: Different therapeutic options have been recommended for the treatment of tuberculosis in HIV-infected patients; however, pharmacokinetic data for these combinations are very limited. Moreover, antituberculous treatment must ideally be given as fixed combinations. Our objective was to evaluate the pharmacokinetic interactions between rifampin (R) and efavirenz (E) in patients with AIDS and tuberculosis.

METHODS: After the diagnosis of tuberculosis, 24 HIV-positive patients were randomized to one of the following treatment groups:

Groups Days 1 - 7 Days 8 - 14
1 H+Z+S + E 600 mg qd + 2NRTI Rifater® + E 600 mg qd + 2NRTI
2 H+Z+S + E 600 mg qd + 2NRTI Rifater® + E 800 mg qd + 2NRTI
3 Rifater® Rifater® + E 800 mg qd + 2NRTI

Rifater (120 mg R, 50 mg H, and 300 mg Z) was administered adjusted to weight: <50 kg, 4 tablets/d; 51-59 kg, 5 tablets/d; and >60 kg, 6 tablets/d. Blood samples were obtained at 0, 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 24 hours on days 7 and 14, and plasma concentrations were quantified by HPLC. Results (µg/ml) were expressed as mean ( SD (range), and the t-test for paired data was used for comparisons.

RESULTS: There were not statistically significative differences when comparing the means of E [Cmax, 2.38 ± 1.02 (0.64-3.58) vs. 2.16 ± 0.55 (1.31-3.03); Cmin, 0.92 ± 0.44 (0.51-1.66) vs. 0.67 ± 0.31 (0.31-1.20); AUC0- -24 (µgh/ml), 35.9 ± 13.6 (25.4-58.7) vs. 28.7 ± 9.40 (17.9-45.0)] and R [Cmax, 5.90 ± 4.41 (1.61-14.07) vs. 5.40 ± 2.70 (3.24-11.3); Cmin, 0.14 ± 0.28 (0.01- 0.84) vs. 1.88 ± 2.15 (0.75-6.71); AUC0-12 (µgh/ml), 27.4 ± 18.2 (9.53-61.0) vs. 31.5 ± 25.9 (6.50-88.2)] on days 7 and 14 in groups 1 and 3, respectively. However, Cmax, Cmin and AUC0-24 of E decreased in 7 of 8 patients by a mean of 30% (5-55%), 24% (7-64%) and 22% (1- 63%) in group 1 after the administration of R. In group C, R levels did not change significantly after the administration of E 800 mg/d. In group 2, E levels were in the therapeutic range in every patient on day 14 [Cmax, 5.40 ± 2.70 (3.24-11.3); Cmin, 1.88 ± 2.15 (0.75-6.71); AUC0-24 (µgh/ml), 46.2 ± 9.72 (34.0-60.2)].

CONCLUSIONS: Concomitant use of R causes a decrease in E concentrations, suggesting that for obtaining therapeutic levels in every patient, it would be advisable to increase the E dose to 800 mg/d.

2001-02-04
32

Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.