A Phenotype–Genotype Approach to Predicting CYP450 and P-Glycoprotein Drug Interactions With the Mixed Inhibitor/Inducer Tipranavir/Ritonavir

The effects of tipranavir/ritonavir (TPV/r) on hepatic and intestinal P-glycoprotein (P-gp) and cytochrome P450 (CYP) enzyme activity were evaluated in 23 volunteers. The subjects received oral (p.o.) caffeine, warfarin + vitamin K, omeprazole, dextromethorphan, and midazolam and digoxin (p.o. and intravenous (i.v.)) at baseline, during the first three doses of TPV/r (500 mg/200 mg b.i.d.), and at steady state. Plasma area under the curve (AUC)0–∞ and urinary metabolite ratios were used for quantification of protein activities. A single dose of TPV/r had no effect on the activity of CYP1A2 and CYP2C9; it weakly inhibited CYP2C19 and P-gp; and it potently inhibited CYP2D6 and CYP3A. Multiple dosing produced weak induction of CYP1A2, moderate induction of CYP2C19, potent induction of intestinal P-gp, and potent inhibition of CYP2D6 and CYP3A, with no significant effects on CYP2C9 and hepatic P-gp. Several P450/transporter single-nucleotide polymorphisms correlated with the baseline phenotype but not with the extent of inhibition or induction. Although mixed induction and inhibition are present, this approach offers an understanding of drug interaction mechanisms and ultimately assists in optimizing the clinical use of TPV/r

The effectiveness of six disinfectants in inactivation of reovirus 3

Reovirus 3 in the presence of foetal bovine serum was exposed to six disinfectants for times of 10, 20 and 30 sec. At the end of such exposure times the addition of skim milk terminated disinfectant activity, and residual virus was assayed using the plaque technique. The six disinfectants considered were Javex (a sodium hypochlorite disinfectant), sodium hydroxide, ethanol, Wescodyne, One Stroke Ves-Phene, and Sonacide. Ethanol (95% v/v) and 1/75 Javex (800 ppm chlorine) were the most effective virucides. Both of these agents inactivated 10(5) plaque forming units (PFU) in 30 sec. Undiluted Sonacide, 0.25% (w/v) sodium hydroxide and 1/200 Wescodyne each inactivated between 10(2) and 10(3) PFU in 30 sec. Javex at a dilution of 1/100 (600 ppm chlorine) was next in effectiveness, inactivating 10(1.5) PFU in 30 sec and was more effective than 1/50 Ves-Phene which inactivated 10(1) PFU in 30 sec. Ethanol in 70% (v/v) solution was totally ineffective in inactivating reovirus 3. Ethanol (95% v/v) after dilution in the test system was 76% (v/v) and ethanol (70% v/v) was really 56% (v/v) The effectiveness of six disinfectants in inactivation of reovirus 3.. Available from: http://www.researchgate.net/publication/16667970_The_effectiveness_of_six_disinfectants_in_inactivation_of_reovirus_3 [accessed Oct 6, 2015]

Variation of functional traits in trees from a biogeographically complex Mexican cloud forest

Background: We report 96- and 144-week follow-up data from VERxVE, demonstrating that nevirapine (NVP) extended release (XR) 400 mg once daily was non-inferior to NVP immediate release (IR) 200 mg twice daily, each administered on a backbone of emtricitabine/tenofovir. Methods: VERxVE was a double-blind, double-dummy, non-inferiority study in adults with screening viral load (VL) >1000 copies/mL and CD4+ cell count <400 cells/mm3 (males) or <250 cells/mm3 (females). Randomisation was stratified by baseline VL (copies/mL) ? 100,000 or >100,000. The primary endpoint was confirmed virologic response (<50 copies/mL) at week 48. Cochran's statistic incorporating baseline VL strata tested non-inferiority of XR efficacy versus IR. Secondary endpoints included 144-week sustained virologic response and safety. Results: In all, 1011 patients were randomised and treated with NVP: 736 (XR n=378; IR n= 358) completed 144 weeks. Virologic response was 63.6% for NVP XR and 58.5% for NVP IR (adjusted difference of 4.8% [95% confidence interval -1.1% to 10.8%] favouring NVP XR). No significant differences were seen in changes in CD4+ T-cell counts from baseline, virologic failures or total discontinuation rates between treatment arms, regardless of demographic or baseline characteristics. Conclusions: NVP XR demonstrated non-inferior virologic efficacy to NVP IR in treatment-naive HIV-infected patients and was well tolerated out to week 144, with a safety profile similar to NVP IR. " 2013 Brinson C, et al.",,,,,,"10.4172/2155-6113.1000233",,,"http://hdl.handle.net/20.500.12104/45675","http://www.scopus.com/inward/record.url?eid=2-s2.0-84884951885&partnerID=40&md5=6b5a7deacf969fec1b71911841c1011f",,,,,,"8",,"Journal of AIDS and Clinical Research",,,,"4",,"Scopus",,,,,,"Clinical trial; Extended-release formulation; Hiv; Nevirapine; Once-daily dosing",,,,,,"Verxve 144-week results: Nevirapine extended release (nvp xr) qd versus nvp immediate release (ir) bid with ftc/tdf in treatment-naive hiv-1 patients",,"Article" "47427","123456789/35008",,"Saldaña-Acosta, A., Departamento de Ecología y Recursos Naturales, Facultad de Ciencias, Universidad Nacional Autónoma de México (UNAM), México, 04510 D.F., Mexico, Instituto Manantlán de Ecología y Biodiversidad, CUCSUR, Universidad de Guadalajara, Autlán de Navarro, 48900 Jalisco, Mexico; Meave, J.A., Departamento de Ecología y Recursos Naturales, Facultad de Ciencias, Universidad Nacional Autónoma de México (UNAM), México, 04510 D.F., Mexico; Paz, H., Centro de Investigaciones en Ecosistemas, UNAM, Morelia, 58190 Michoacán, Mexico; Sánchez-Velásquez, L.R., Instituto de Biotecnología y Ecología Aplicada, Dirección General de Investigaciones, Universidad Veracruzana, Xalapa, Veracruz, Mexico; Villaseñor, J.L., Departamento de Botánica, Instituto de Biología, UNAM, México, 04510 D.F., Mexico; Martínez-Ramos, M., Centro de Investigaciones en Ecosistemas, UNAM, Morelia, 58190 Michoacán, Mexico",,"Saldana-Acosta, A