Renal excretion of emtricitabine II. Effect of trimethoprim on emtricitabine excretion: In vitro and in vivo studies

Allen

Journal of Clinical Pharmacy and Therapeutics

et al. 2010

Section: Resultsmentioning

confidence: 99%

Section: Safetymentioning

confidence: 91%

Evaluation of steady-state pharmacokinetic interactions between ritonavir-boosted BILR 355, a non-nucleoside reverse transcriptase inhibitor, and lamivudine/zidovudine in healthy subjects

Allen

Journal of Clinical Pharmacy and Therapeutics

et al. 2010

“…It was found that PBC, TEA and URD had no effect on FTC excretion, but CMD decreased FTC excretion by two times. The result suggested FTC renal transport is likely mediated by CMD‐sensitive human organic cation transporters (hOCT) in the kidney, which is thought to be related to OCT2 [25,26]. The latest published data show that FTC also interacts with hOCT1, hOCT2 and hOCT3 in a cell culture system [27], suggesting that FTC is a potential substrate of hOCT1 and hOCT3 as well.…”

Section: Discussionmentioning

confidence: 99%

Concomitant Administration of BILR 355/r with Emtricitabine/Tenofovir Disoproxil Fumarate Increases Exposure to Emtricitabine and Tenofovir: A Randomized, Open-Label, Prospective Study

Scholl

Basic &Amp; Clinical Pharmacology &Amp; Toxicology

et al. 2010

The objective of this study was to evaluate the pharmacokinetic interaction of ritonavir-boosted BILR 355 (BILR 355 ⁄ r) with emtricitabine (FTC) ⁄ tenofovir disoproxil fumarate (TDF). This was an open-label, prospective study. For Group A, 26 healthy subjects were given FTC ⁄ TDF (200 ⁄ 300 mg) once daily (QD) for 7 days and then co-administered with BILR 355 ⁄ r (150 ⁄ 100 mg) twice daily (bid) for an additional 7 days. Pharmacokinetics assessments were performed at days 7 and 14. For Group B, eight subjects were given BILR 355 ⁄ r (150 ⁄ 100 mg) bid for 7 days. The pharmacokinetic data from Group B were also pooled with Group B subjects from other similar studies performed in parallel to this study. After co-administration with BILR 355 ⁄ r, the geometric mean ratio (GMR, %) and 90% confidence interval (CI, %) of combined versus alone treatment for FTC AUC 0-24,ss , C max,ss and C 0-12,ss were 160 (154-166), 128 (121-136) and 223 (206-241), respectively; and for tenofovir AUC 0-24,ss , C max,ss and C 24,ss were 126 (121-132), 131 (117-146) and 132 (124-140), respectively. Co-administration with FTC ⁄ TDF resulted in an 18% increase in AUC 0-12,ss , 14% increase in C max,ss and 19% increase in C 12,ss for BILR 355. BILR 355 was well tolerated in this study. There was no evidence of increased risk of TFV or FTC toxicity upon co-administration of FTC ⁄ TDF with BILR 355 ⁄ r.Highly active antiretroviral therapy (HAART), antiretroviral therapy that combines three or more anti-human immunodeficiency virus (HIV)-1 agents, has proven to be effective in reducing viral load and HIV-1-related mortality and morbidity [1,2]. The recommended HAART often includes a dual nucleoside reverse-transcriptase inhibitors (NRTI) 'backbone' with the addition of a protease inhibitor or nonnucleoside reverse transcriptase inhibitor. TRUVADA Ò (Gilead, Foster City, CA, USA) tablets are fixed-dose combination tablets containing emtricitabine (FTC) (200 mg) and tenofovir disoproxil fumarate (TDF) (300 mg). FTC is a synthetic nucleoside analogue of cytidine. Tenofovir DF or TDF, a prodrug of tenofovir, is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analogue of adenosine 5¢-monophosphate [3]. Both FTC and tenofovir exhibit inhibitory activity against HIV-1 reverse transcriptase and show good efficacy in combating HIV-1 infection. In addition, the FTC ⁄ TDF fixed-dose combination displays a superior safety profile compared with thymidine analogues. After oral administration, FTC is rapidly and nearly completely absorbed, and the systemic FTC is preliminarily eliminated by renal excretion, with 60-70% of an oral dose excreted in urine as unchanged drug. After oral administration, TDF is rapidly absorbed and converted to the active form, tenofovir.Urinary excretion is the predominant elimination pathway, with approximately 70-80% of the intravenous dose recovered as unchanged drug in the urine. The renal excretion of both FTC and tenofovir is through a combination of glomerular filtration and active...

Journal of Pharmacy and Pharmacology

“…Additional studies assessed rigosertib systemic exposure during and after intestinal perfusion. The day before experimentation, the jugular vein of the rat was cannulated using a published method . The experiment involved intestinal perfusion of rigosertib for 60 min, with blood samples taken from the jugular vein at 5, 10, 15, 30, 45, 60, 65, 75, 85, 95 and 105 min after perfusion initiation.…”

Section: Methodsmentioning

confidence: 99%

Determination of intestinal permeability of rigosertib (ON 01910.Na, Estybon): correlation with systemic exposure

White

Babayeva

Taft

et al. 2013