The effect of lopinavir/ritonavir (LPV/r) administration on cytochrome P450 (CYP) enzyme activity was quantified using a phenotyping biomarker cocktail. Changes in CYP2C9, CYP2C19, CYP3A, CYP1A2, N-acetyltransferase-2 (NAT-2), and xanthine oxidase (XO) activities were evaluated warfarin (WARF) + vitamin K, omeprazole (OMP), intravenous (IV) oral (PO) midazolam (MDZ), caffeine (CAF).: Open-label, multiple-dose, pharmacokinetic study healthy volunteers.Subjects (n = 14) simultaneously received...

Lopinavir, an HIV protease inhibitor, is coformulated with ritonavir to enhance the bioavailability and pharmacokinetics of lopinavir. The original solid oral formulation lopinavir/ritonavir, a soft-gelatin capsule (SGC), requires refrigerated storage, taken as 6 capsules daily at recommended adult dose, administered food maximize Melt extrusion technology was used produce tablet reducing number dosage units per day simplifying storage requirements. Three studies assessed doses...

Elagolix is a nonpeptide, oral gonadotropin-releasing hormone (GnRH) antagonist being developed for sex-hormone–dependent diseases in women. We evaluated the pharmacokinetics and pharmacodynamics of elagolix. This study was randomized, double-blind, placebo-controlled, multiple-ascending dose 45 healthy premenopausal women at research unit. [150 mg once daily or 100, 200, 300, 400 twice (BID)] placebo administered 21 days. Main outcome measures were elagolix pharmacokinetics, suppression...

Objective The objective of the study was to develop and validate a population pharmacokinetic model for irinotecan 2 its metabolites, SN-38 glucuronide (SN-38G). Methods Plasma concentrations were obtained during up 48 hours after 90-minute continuous intravenous infusion (100–340 mg/m2) in 78 patients. Data splitting used create model-building model-validation data sets. Pharmacokinetic parameter estimates by compartmental methods describe disposition metabolites that are dependent on...

Pharmacokinetic models were developed to describe the disposition of markers extracellular fluid (inulin) and total body water (antipyrine) from moment injection incorporate intravascular mixing component, determined by a marker space (indocyanine green, ICG). The simultaneous dispositions these characterized in four halothane-anesthetized dogs. After ICG, [14C]-inulin, antipyrine into right atrium, femoral arterial blood samples collected every 3 sec for 1 min less frequently 20 ICG 360...

Paritaprevir is a direct acting antiviral agent for use as part of multidrug hepatitis C virus infection treatment regimen. To characterize the pharmacokinetics, safety, and tolerability paritaprevir determine an optimal dosing regimen subsequent evaluations, clinical studies were conducted with alone or ritonavir, cytochrome P450 3A4 inhibitor anticipated to increase exposure.

PURPOSE: The goals of this study were to determine the maximum-tolerated dose and describe toxicities combination irinotecan docetaxel administered every 3 weeks patients with advanced malignancies and, also, evaluate effect on disposition preliminary evidence antitumor activity. PATIENTS AND METHODS: Eighteen received 85 courses (median, two courses; range, one 15 courses) treatment irinotecan, over 90 minutes by intravenous infusion, followed docetaxel, 60 infusion. Four escalating levels...

A total of 71 HIV-negative healthy adults were randomized to 1 6 regimens receive lopinavir/ritonavir tablets 400/100 mg twice daily (bid) or 800/200 once (qd) atazanavir 300 + ritonavir 100 qd from study days 15 with a moderate-fat meal. One hour before breakfast, either omeprazole 40 was administered on 11 through 15, single dose ranitidine 150 day 11. Lopinavir, atazanavir, and pharmacokinetics determined 10, 11, compared using point estimates 90% confidence intervals (CIs). The for...

Inhibitors of hepatitis C virus (HCV) protease have shown marked antiviral activity in short-term clinical studies HCV-infected individuals. The interaction the investigational HCV inhibitors VX-950 and SCH 503034 with ritonavir, a potent inhibitor cytochrome P450 3A, was studied vitro vivo. In rat human liver microsomes, metabolism strongly inhibited by presence 4 microM ritonavir. Upon co-dosing either or ritonavir rats, plasma exposure increased > 15-fold, concentrations 8 h after dosing...

Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus developed for the treatment chronic plaque psoriasis. induces cytochrome P450 (CYP) 3A4 while inhibiting P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, and OATP1B3 in vitro. Static drug-drug interactions (DDIs) predictions suggested possible clinical induction CYP3A4, inhibition P-gp, BCRP, OATP1B1, leading to challenges interpreting DDI...

Abstract Context Elagolix is an oral gonadotropin-releasing hormone (GnRH) antagonist recently approved for the treatment of endometriosis-associated pain and being developed heavy menstrual bleeding associated with uterine fibroids. Objective The objective was to evaluate effects elagolix on ovulation ovarian sex hormones. Design Setting This a randomized, open-label, multicenter study. Participants were healthy ovulatory women aged 18 40 years. Interventions administered orally 3...

Background The cardiovascular effects of halothane are well recognized, but little is known how this affects drug distribution. effect anesthesia on physiologic factors that affect disposition from the moment injection was investigated. Methods dispositions markers intravascular space and blood flow (indocyanine green), extracellular free water diffusion (inulin), total body tissue perfusion (antipyrine) were determined in four purpose-bred coonhounds. dogs studied while awake anesthetized...

Objective: To investigate the efficacy and safety of high-dose lopinavir/ritonavir (LPV/r) therapy in multiple protease inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced subjects. Method: Thirty-six HIV-1-infected subjects were randomized to LPV/r 400/300 mg or 667/167 bid a 48-week, open-label study. Subjects also received investigator-selected nucleoside inhibitors (NRTIs). Primary outcomes proportion with HIV-1 RNA levels <50 copies/mL at week 24 time until...

Previous studies have demonstrated that lopinavir/ritonavir monotherapy maintained plasma HIV-1 RNA suppression in a large proportion of antiretroviral naive subjects. However, more subjects receiving experienced confirmed virologic rebound >50 copies/ml compared to standard three-drug HAART regimen. In this study, we sought determine the factors associated with maintenance monotherapy. Antiretroviral-naive HIV-1-infected volunteers were randomized 2:1 initiate lopinavir/ritonavir-based...

Abstract The aim of these studies was to assess the safety and pharmacokinetics elagolix, an oral nonpeptide gonadotropin‐releasing hormone antagonist following administration in women with renal or hepatic impairment. Two phase 1 were conducted adult normal function versus impairment (reduced study), (full study design). All received a single dose elagolix 200 mg (renal) 150 (hepatic). Intensive pharmacokinetic blood samples collected. Elagolix exposures comparable those moderate/severe...

To assess the safety, efficacy and metabolic toxicity of lopinavir/ritonavir + saquinavir or zidovudine/lamivudine evaluate pharmacokinetics saquinavir.HIV-1-infected, antiretroviral-naive subjects were randomized to (400/100 mg) twice daily (800 (150/300 in a Phase II, 48 week study. Subjects receiving initiated escalating doses (400, 600 800 weekly for 3 weeks.By intent-to-treat (non-completer = failure) analysis, 10/16 (63%) saquinavir-treated 7/14 (50%) zidovudine/lamivudine-treated...

Background A novel ritonavir oral powder formulation has been developed to eliminate the alcohol and propylene glycol contents in current solution for paediatric use. Two clinical studies were conducted assess bioequivalence of marketed evaluate effect food vehicles on bioavailability. Methods Study 1 was a randomized, partial-crossover, 4-period study 48 subjects. Regimens included: under moderate-fat conditions, water fasting, or high-fat chocolate milk pudding conditions. 2 crossover, 24...

ABSTRACT Lopinavir-ritonavir is frequently prescribed to HIV-1-infected women during pregnancy. Decreased lopinavir exposure has been reported pregnancy, but the clinical significance of this reduction uncertain. This analysis aimed evaluate need for dose adjustment We conducted a population pharmacokinetic and ritonavir concentrations collected from 84 pregnant 595 nonpregnant treatment-naive -experienced subjects enrolled in six studies. doses studies ranged between 400/100 600/150 mg...

Background The parasitic filariae responsible for onchocerciasis and lymphatic filariasis are host to an endosymbiotic bacterium, Wolbachia , which is essential the fertility development of parasites. We performed a Phase-I pharmacokinetic, safety food-effect study on single multiple ascending doses flubentylosin (ABBV-4083), macrolide antibacterial with activity against intended sterilize eliminate Methods Seventy-eight healthy adults were exposed flubentylosin; 36 40, 100, 200, 400 or 1000...