LPV/r therapy results in modest induction of CYP1A2 and CYP2C9 and potent induction of CYP2C19 activity. Increasing doses of concomitant medications metabolized by these enzymes may be necessary. LPV/r inhibited intestinal CYP3A to a greater extent than hepatic CYP3A activity. Doses of concomitant CYP3A substrates should be reduced when combined with LPV/r, although intravenously administered compounds may require less of a relative dose reduction than orally administered compounds.

No abstract

In stably suppressed patients, 200 mg emtricitabine QD was equivalent to 150 mg lamivudine BID. Emtricitabine-containing HAART was associated with a high rate of sustained virologic suppression during 4 years of follow-up.

Highly active antiretroviral therapy (HAART) for human immunodeficiency virus-1 (HIV-1) and prophylactic therapy for opportunistic infections have increased survival. Adverse effects of HAART include lipid profile alterations, diabetes mellitus, and fat redistribution. These metabolic and physical changes are called the HIV-associated lipodystrophy syndrome. A link to protease inhibitors has been suggested, and more recently to nucleoside reverse transcriptase inhibitors and factors related to duration of HIV-1 infection itself.

No abstract

Hospitalized patients with gram-negative infections are often treated with combination antimicrobial agents; however, some of the recently available data, although limited, suggest that administration of monotherapy is a feasible alternative in certain patient populations.

Purpose-The effects of omeprazole on indinavir when administered alone or in combination with ritonavir were evaluated.Methods-Fourteen men and women age 18-55 years not infected with human immunodeficiency virus who met study qualifications were randomized to receive placebo, 20 mg of omeprazole, or 40 mg of omeprazole daily. After seven days, the single-dose pharmacokinetic profile of an 800-mg dose of indinavir alone or in combination with 200 mg of ritonavir was evaluated. Study participants received each of four study regimens in one of four randomly assigned orders. Blood samples were collected, and plasma indinavir and ritonavir concentrations were analyzed using high-performance liquid chromatography. Conclusion-The AUC of indinavir was substantially decreased in healthy volunteers who received omeprazole 20 or 40 mg daily for seven days before the administration of a single 800-mg dose of indinavir. Concomitant administration of ritonavir 200 mg with indinavir in participants receiving omeprazole led to a significant increase in the AUC of indinavir. Results-The Index termsAntiretroviral agents; Blood levels; Dosage; Drug interactions; Gastrointestinal drugs; HIV infections; Indinavir; Omeprazole; Pharmacokinetics; Ritonavir Protease inhibitors (PIs) exhibit a high degree of pharmacokinetic variability in patients infected with the human immunodeficiency virus (HIV). 1,2 Large interindividual differences in drug absorption and elimination in HIV-infected patients have been primarily attributed to constitutive or altered drug metabolizing enzymes, P-glycoprotein transporter activities, and poor drug solubility. 3 With the PIs indinavir and atazanavir, changes in gastric pH can alter drug absorption. 4,5 Specifically, when these PIs are administered with medications that Address correspondence to Dr. Kashuba at the School of Pharmacy, CB7360, University of North Carolina, Chapel Hill, NC 27599-7360 (akashuba@unc.edu increase gastric pH, such as histamine (H 2 )-receptor antagonists and proton-pump inhibitors (PPIs), bioavailability can decrease by up to 76%. 4,6 A survey of 200 HIV-infected patients was performed to assess their use of drugs that affect gastric acidity. 7 Fifty-six percent of HIV-infected patients who had recently begun highly active antiretroviral therapy (HAART) had taken nonprescription acid-reducing agents, and 39% had used both nonprescription and prescription products for acid reduction. Forty-six percent of patients on a PI-containing regimen had used PPIs or H 2 -receptor antagonists once they started HAART, and 35% had used them within the previous 12 months. This widespread use of acid-reducing agents among HIV-infected patients has implications for drug interactions with antiretrovirals and other medications that require an acidic environment for adequate dissolution and absorption.Ritonavir is a cytochrome P-450 (CYP) isoenzyme 3A and P-glycoprotein inhibitor which, when used in low doses, can increase the exposure of concomitantly administered PIs. The concomitant ad...

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