Lopez-Cortes LF, Ruiz R, Viciana P, Alarcon A, Leon E, Sarasa M, Lopez-Pua Y, Gomez J, Pachon J; Conference on Retroviruses and Opportunistic Infections.

Program Abstr 8th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 8th 2001 Chic Ill. 2001 Feb 4-8; 8: 52 (abstract no. 32).

Hosp Virgen del Rocio, Sevilla.

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: [table: see text] 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 (microgram/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 [C(max), 2.38 +/- 1.02 (0.64-3.58) vs. 2.16 +/- 0.55 (1.31-3.03); C(min), 0.92 +/- 0.44 (0.51-1.66) vs. 0.67 +/- 0.31 (0.31-1.20); AUC0- -24 (microgramh/ml), 35.9 +/- 13.6 (25.4-58.7) vs. 28.7 +/- 9.40 (17.9-45.0)] and R [C(max), 5.90 +/- 4.41 (1.61-14.07) vs. 5.40 +/- 2.70 (3.24-11.3); C(min), 0.14 +/- 0.28 (0.01- 0.84) vs. 1.88 +/- 2.15 (0.75-6.71); AUC0-12 (microgramh/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, C(max), C(min) 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 [C(max), 5.40 +/- 2.70 (3.24-11.3); C(min), 1.88 +/- 2.15 (0.75-6.71); AUC0-24 (microgramh/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.

Publication Types:

• Meeting Abstracts

Keywords:

• Acquired Immunodeficiency Syndrome
• Drug Interactions
• HIV Infections
• HIV Seropositivity
• Humans
• Oxazines
• Pyrazinamide
• Rifampin
• Rifater
• Tuberculosis
• efavirenz
• pharmacokinetics

Other ID:

• GWAIDS0006315

UI: 102243811

From Meeting Abstracts