Oral versus Intravenous Antibiotics for Bone and Joint Infection.

Background: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication.

Methods: We enrolled adults who were being treated for bone or joint infection at 26 U.

Effect of intermittent rifampicin on the pharmacokinetics and safety of raltegravir.

Objectives: Previous studies of raltegravir and rifampicin have not studied the interaction when rifampicin is dosed intermittently. This study aimed to assess the pharmacokinetics of twice daily raltegravir and intermittently dosed rifampicin.

Methods: This was a prospective, open, single-arm, three-part, controlled study in healthy volunteers.

The relationship between nevirapine plasma concentrations and abnormal liver function tests.

Abnormal liver function tests are frequently observed in HIV-infected individuals receiving nevirapine (NVP). Here we investigate the relationship between total and unbound plasma concentrations of NVP and the liver enzymes alanine aminotransferase (ALT) and gamma-glutamyl transferase (gammaGT). HIV-infected individuals [n = 85, 22 female, 34 hepatitis C or B virus (HCV or HBV(+))] receiving NVP (200 mg bd; median duration 66 weeks, range 3-189) and two nucleoside reverse transcriptase inhibitors (NRTIs) were enrolled into this study.

Pharmacokinetics of saquinavir co-administered with cimetidine.

The present study evaluated the effect of cimetidine, a histamine H(2) receptor antagonist able to inhibit cytochrome P450 metabolism, on the steady-state pharmacokinetics of saquinavir soft gel. Twelve healthy volunteers (eight males and four females) participated in an open-label, double-phase pharmacokinetic study. Volunteers took saquinavir soft gel 1200 mg three times a day for 13 days and then saquinavir soft gel 1200 mg twice a day with cimetidine 400 mg twice a day from day 14 to 26.

Clinical use of lopinavir/ritonavir in a salvage therapy setting: pharmacokinetics and pharmacodynamics.

Lopinavir/ritonavir was administered to 35 HIV-infected patients after therapeutic failure with other protease inhibitors. The pharmacokinetics (trough concentrations) and baseline viral genotype were determined, together with the immunovirological outcome. The 22 responders had significantly higher mean lopinavir concentrations and lower baseline numbers of mutations.

Simultaneous determination of rifampicin and efavirenz in plasma.

Complex drug interactions involving antiretroviral agents and drugs for the management of opportunistic infections demand the monitoring of plasma drug concentrations to prevent treatment failure. The high occurrence of tuberculosis in HIV-infected subjects makes the management of HIV treatment complex. Rifampicin, a potent inducer of the cytochrome P 450 metabolic pathway, is a very active antituberculosis drug that accelerates the metabolism of protease inhibitors.

The unbound percentage of saquinavir and indinavir remains constant throughout the dosing interval in HIV positive subjects.

Aims: To measure the unbound plasma concentrations of saquinavir (SQV) and indinavir (IDV) and to relate them to the total plasma concentrations in order to establish the unbound percentage of protease inhibitors in vivo during a full dosage interval profile.

Methods: HIV-infected subjects (n = 35; median CD4 cell count = 340 x 10(6) cells l-1, range: 120-825; viral load < 50 copies ml-1 in 22/35) treated with SQV or IDV containing regimens were studied. Plasma drug samples were collected at 0, 2, 4, 8 and 12 h postdose for the twice daily regimens and 0, 1, 2, 4 and 8 h for the three times daily regimens.