Pharmacokinetics of indinavir/ritonavir (800/100 mg) in combination with efavirenz (600 mg) in HIV-1-infected subjects. 2003

Mark A Boyd, and Rob E Aarnoutse, and Kiat Ruxrungtham, and Michael Stek, and Rolf P G van Heeswijk, and Joep M A Lange, and David A Cooper, and Praphan Phanuphak, and David M Burger
The HIV Netherlands Australia Thailand Research Collaboration, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand. mark.bo@chula.ac.th

BACKGROUND Addition of efavirenz (600 mg) to indinavir/ritonavir (800/100 mg) results in significant decreases in indinavir levels in healthy volunteers. This study evaluated the steady-state pharmacokinetics of indinavir/ritonavir at 800/100 mg twice daily (bid) in combination with efavirenz at 600 mg once daily (qd) in HIV-infected Thai subjects who used this nucleoside-sparing combination in The HIV Netherlands Australia Thailand Research Collaboration 009 study. METHODS At week 4 of the study, 12-hour pharmacokinetic profiles for indinavir/ritonavir were obtained for 20 HIV-infected subjects. For efavirenz, the concentrations at 12 hours and 24 hours (Cmin) after dosing were assessed. RESULTS All subjects (10 males and 10 females) completed the study. The geometric mean area under the concentration versus time curve, Cmin, and maximum plasma concentration of indinavir were 45.7 mg/(L. h) (95% confidence interval [CI], 39.8-52.5), 0.32 mg/L (95% CI, 0.24-0.44), and 11.1 mg/L (95% CI, 9.4-13.0), respectively. A >10-fold variation in indinavir Cmin was observed. All subjects had an indinavir Cmin that was at least comparable with the reported mean population Cmin of indinavir at 800 mg thrice daily without ritonavir (0.15 mg/L). The geometric mean concentration at 12 hours and Cmin of efavirenz were 3.1 mg/L (95% CI, 2.5-3.7) and 2.1 mg/L (95% CI, 1.6-2.6), respectively. CONCLUSIONS Despite the known pharmacokinetic interaction between efavirenz and indinavir/ritonavir, the combination of indinavir/ritonavir at 800/100 mg bid and efavirenz at 600 mg qd results in adequate minimum concentrations of both indinavir and efavirenz for treatment-naive patients.

UI MeSH Term Description Entries
D008297 Male Males
D010078 Oxazines Six-membered heterocycles containing an oxygen and a nitrogen.
D003521 Cyclopropanes Three-carbon cycloparaffin cyclopropane (the structural formula (CH2)3) and its derivatives.
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000163 Acquired Immunodeficiency Syndrome An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000480 Alkynes Hydrocarbons with at least one triple bond in the linear portion, of the general formula Cn-H2n-2. Acetylenic Compounds,Alkyne,Acetylenes
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human

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