Pharmacokinetics of darunavir/ritonavir and rifabutin coadministered in HIV-negative healthy volunteers.

The drug-drug interaction between rifabutin (RFB) and darunavir/ritonavir (DRV/r) was examined in a randomized, three-way crossover study of HIV-negative healthy volunteers who received DRV/r 600/100 mg twice a day (BID) (treatment A), RFB 300 mg once a day (QD) (treatment B), and DRV/r 600/100 mg BID plus RFB 150 mg every other day (QOD) (treatment C). The sequence of treatments was randomized, and each treatment period lasted 12 days. Full pharmacokinetic profiles were determined for DRV, ritonavir, and RFB and its active metabolite, 25-O-desacetylrifabutin (desRFB), on day 13.

Efficacy and safety of prucalopride in patients with chronic noncancer pain suffering from opioid-induced constipation.

Background: Opioid-induced constipation (OIC) has negative effects on quality of life (QOL). Prucalopride is a new, selective 5-HT(4) agonist and enterokinetic with strong clinical data in chronic constipation. This study investigated the efficacy, safety, and tolerability of prucalopride in patients with noncancer pain and OIC.

Pharmacokinetics of multiple-dose darunavir in combination with low-dose ritonavir in individuals with mild-to-moderate hepatic impairment.

Background And Objective: The pharmacokinetics of some HIV protease inhibitors are altered in patients with hepatic impairment. The TMC114-C134 study assessed the pharmacokinetics and safety of darunavir/ritonavir 600 mg/100 mg twice daily in HIV-negative subjects with hepatic impairment (defined according to Child-Pugh classification A [mild] or B [moderate]) compared with matched, HIV-negative, healthy subjects.

Methods: All subjects received darunavir/ritonavir 600 mg/100 mg twice daily for 6 days with a morning dose on day 7.

Pharmacokinetic interaction between indinavir and darunavir with low-dose ritonavir in healthy volunteers.

Objective: To investigate the potential for a pharmacokinetic interaction between darunavir (DRV, TMC114, Prezista), indinavir (IDV, Crixivan) and low-dose ritonavir (RTV, Norvir).

Methods: In three 7-day sessions, 17 HIV-negative healthy volunteers received treatment A (DRV/r 400/100 mg b.i.

Pharmacokinetic interaction between nevirapine and darunavir with low-dose ritonavir in HIV-1-infected patients.

Aim: To investigate the pharmacokinetic interaction between darunavir/ritonavir (DRV/r) and nevirapine (NVP) in 19 HIV-infected patients.

Methods: An open-label, randomized, crossover study. Patients received Treatment A [NVP 200 mg b.

Pharmacokinetic interaction between ethinyl estradiol, norethindrone and darunavir with low-dose ritonavir in healthy women.

Background: An open-label, randomized, crossover study was performed to investigate the effect of multiple doses of darunavir co-administered with low-dose ritonavir (DRV/r) on the steady-state pharmacokinetics of the oral contraceptives ethinyl estradiol (EE) and norethindrone (NE) (commercial name of the combined drug Ortho-Novum 1/35) in 19 HIV-negative healthy women.

Methods: In session 1, participants received 35 microg EE and 1.0 mg NE from days 1 to 21.

Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48.

Background: The present primary analysis of AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects (ARTEMIS) compares the efficacy and safety of once-daily darunavir/ritonavir (DRV/r) with that of lopinavir/ritonavir (LPV/r) in treatment-naive patients.

Methods: Patients with HIV-1 RNA at least 5000 copies/ml were stratified by HIV-1 RNA and CD4 cell count in a phase III, open-label trial, and randomized to receive DRV/r 800/100 mg qd or LPV/r 800/200 mg total daily dose (bid or qd) plus fixed-dose tenofovir and emtricitabine for 192 weeks. The primary objective was to demonstrate non-inferiority of DRV/r as compared with LPV/r in HIV-1 RNA less than 50 copies/ml per-protocol time-to-loss of virologic response at 48 weeks.

Pharmacokinetics of darunavir/ritonavir and ketoconazole following co-administration in HIV-healthy volunteers.

Aims: To investigate the interaction between ketoconazole and darunavir (alone and in combination with low-dose ritonavir), in HIV-healthy volunteers.

Methods: Volunteers received darunavir 400 mg bid and darunavir 400 mg bid plus ketoconazole 200 mg bid, in two sessions (Panel 1), or darunavir/ritonavir 400/100 mg bid, ketoconazole 200 mg bid and darunavir/ritonavir 400/100 mg bid plus ketoconazole 200 mg bid, over three sessions (Panel 2). Treatments were administered with food for 6 days.

Darunavir/ritonavir pharmacokinetics following coadministration with clarithromycin in healthy volunteers.

This study investigated the steady-state pharmacokinetic interaction between the HIV protease inhibitor, darunavir (TMC114), administered with low-dose ritonavir (darunavir/ritonavir), and clarithromycin in HIV-negative healthy volunteers. In a 3-way crossover study, 18 individuals received darunavir/ritonavir 400/100 mg bid, clarithromycin 500 mg bid, and darunavir/ritonavir 400/100 mg bid plus clarithromycin 500 mg bid in 3 separate sessions for 7 days, with a washout period of at least 7 days between treatments. Pharmacokinetic assessment was performed on day 7.

Pharmacokinetic interaction between darunavir and saquinavir in HIV-negative volunteers.

This was an open-label, crossover study to investigate the pharmacokinetic interaction between darunavir (TMC114), coadministered with low-dose ritonavir (darunavir/ritonavir), and the protease inhibitor saquinavir in HIV-negative healthy volunteers. Thirty-two volunteers were randomized into two cohorts (panel 1 and panel 2). In two separate sessions, panel 1 received 400/100 mg darunavir/ritonavir twice a day and 400/1000/100 mg darunavir/saquinavir/ritonavir twice a day; panel 2 received 1000/100 mg saquinavir/ritonavir twice a day and 400/1000/100 mg darunavir/saquinavir/ritonavir twice a day.

Pharmacokinetic interaction between TMC114/r and efavirenz in healthy volunteers.

Background: This open-label, crossover study investigated the pharmacokinetic interaction between TMC114 (darunavir [Prezista]), administered with low-dose ritonavir (TMC114/r) and efavirenz (EFV) in HIV-negative, healthy volunteers.

Methods: Volunteers received TMC114/r 300/100 mg twice daily for 6 days, and once daily on day 7 (session 1). After a 7-day washout period volunteers received EFV 600 mg once daily for 18 days (session 2), with coadministration of TMC114/r 300/100 mg twice daily from day 11-day 16 and TMC114/r once daily on day 17.

Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial.

Background: The protease inhibitor darunavir has been shown to be efficacious in highly treatment-experienced patients with HIV infection, but needs to be assessed in patients with a broader range of treatment experience. We did a randomised, controlled, phase III trial (TITAN) to compare 48-week efficacy and safety of darunavir-ritonavir with that of lopinavir-ritonavir in treatment-experienced, lopinavir-naive patients.

Methods: Patients received optimised background regimen plus non-blinded treatment with darunavir-ritonavir 600/100 mg twice daily or lopinavir-ritonavir 400/100 mg twice daily.

Pharmacokinetic interaction between TMC114/ritonavir and tenofovir disoproxil fumarate in healthy volunteers.

Aim: TMC114 is a new HIV protease inhibitor, used in combination with low-dose ritonavir (TMC114/r) as a pharmacokinetic enhancer. Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor. Both antiretrovirals show activity against wild-type and resistant HIV.

Pharmacokinetics of darunavir (TMC114) and atazanavir during coadministration in HIV-negative, healthy volunteers.

Background And Objective: To investigate the potential for pharmacokinetic interactions between the protease inhibitors darunavir (DRV, TMC114) coadministered with low-dose ritonavir (darunavir/r), and atazanavir in HIV-negative, healthy volunteers.

Methods: This was an open-label, randomised, three-period, crossover study. Darunavir/r (400/100mg twice daily), atazanavir/r (300/100mg once daily) or darunavir/r (400/100mg twice daily) plus atazanavir (300mg once daily) were administered in three separate sessions, with a washout period of at least 7 days between regimens.

The effect of different meal types on the pharmacokinetics of darunavir (TMC114)/ritonavir in HIV-negative healthy volunteers.

This open-label, randomized, crossover study investigated the bioavailability, short-term safety, and tolerability of darunavir (TMC114) coadministered with low-dose ritonavir under fasted conditions and after different meal types in HIV-negative healthy volunteers. All volunteers received ritonavir 100 mg twice daily on days 1 to 5, with a single darunavir 400-mg tablet given on day 3 (darunavir/rtv). Pharmacokinetic parameters for darunavir and ritonavir were determined under fasted conditions and following a standard breakfast, a high-fat breakfast, a nutritional protein-rich drink, or a croissant with coffee.

Pharmacokinetic interaction between darunavir boosted with ritonavir and omeprazole or ranitidine in human immunodeficiency virus-negative healthy volunteers.

Darunavir (DRV; TMC114; Prezista) is a human immunodeficiency virus (HIV) protease inhibitor used in combination with low-dose ritonavir (RTV) (DRV/r) as a pharmacokinetic enhancer. Protease inhibitor absorption may be decreased during coadministration of drugs that limit stomach acid secretion and increase gastric pH. This study was conducted to investigate the effect of ranitidine and omeprazole on the plasma pharmacokinetics of DRV and RTV in HIV-negative healthy volunteers.

Prucalopride is effective in patients with severe chronic constipation in whom laxatives fail to provide adequate relief. Results of a double-blind, placebo-controlled clinical trial.

Background: Chronic constipation (CC) is common and there is a need for more effective and better-tolerated agents that normalize bowel function without affecting secretion. Prucalopride is a novel, selective serotonin(4) receptor agonist with enterokinetic properties.

Aims: Pilot study to compare the efficacy and tolerability of prucalopride and placebo in patients with severe CC referred to a tertiary centre.