Report on 11th EACS, Madrid, October 2007 Drug Interaction Studies presented at the 11th European AIDS Conference, Madrid, October 2007 The following drug interaction studies are summarised in this report. Abstract Interactions between two or more anti-HIV drugs Abstracts and posters may be available – please checkfor further information. Report on 11th EACS, Madrid, October 2007 Interactions between two or more anti-HIV drugs Lack of pharmacokinetic interaction of tenofovir and emtricitabine on nevirapine. Davis JrC, Gillam B, Amoroso A, et al. Abstract P4.1/03 The effect of tenofovir/emtricitabine on the pharmacokinetics of nevirapine (200 mg twice daily) was studied in 7 HIV+, African-American subjects. The mean ± sd steady state nevirapine Cmin was 4971 ± 1985 ng/ml and was comparable to historical values. The mean nevirapine Cmin after the 200 mg once daily 2 week lead-in phase was also determined and was 2876 ng/ml. An open randomised two period crossover study in 2 cohorts to investigate the effect of steady state TMC125 and the combination of TMC125/DRV/r on the steady state pharmacokinetics of oral maraviroc in healthy subjects. Davis J, Scholler-Gyure M, Kakuda TN, et al. Abstract P4.3/02. The pharmacokinetics of maraviroc and etravirine were determined in HIV- subjects following coadministration of etravirine (200 mg twice daily) and maraviroc (300 mg twice daily) or coadministration of etravirine (200 mg twice daily, maraviroc (150 mg twice daily) and darunavir/ritonavir (600/100 mg twice daily). Coadministration of etravirine decreased maraviroc AUC and Cmax by 53% and 60% respectively; coadministration of etravirine, darunavir and ritonavir increased maraviroc AUC and Cmax by 210% and 77% respectively. Maraviroc had no significant effect on etravirine, darunavir or ritonavir pharmacokinetics. When maraviroc is coadministered with etravirine, in the absence of a potent CYP3A4 inhibitor, the recommended dose of maraviroc is 600 mg twice daily. Impact of demographic factors and tenofovir coadministration on atazanavir trough plasma concentration in HIV infected patients treated with boosted atazanavir. Lescure F-X, Poirier J-M, Meynard J-L, et al. Abstract P4.3/06. Factors affecting atazanavir trough concentrations were determined in a cohort of 128 HIV+ subjects receiving atazanavir/ritonavir (300/100 mg once daily) with two nucleos/tide inhibitors. Tenofovir was administered to approximately half of the cohort and was found not to influence atazanavir Cmin (525 vs 402 ng/ml, alone vs with tenofovir; p=0.2). There was no impact of age, gender, weight or BMI on atazanavir concentrations; however, concentrations were significantly higher (p=0.04) in non-Caucasians (562 ng/ml) than in Caucasians (418 ng/ml). Interactions between anti-HIV drugs and other drugs Pharmacokinetics of zidovudine and lamivudine under oral uridine supplementation with NucleomaxX. Venhoff N, Venhoff AC, Jayewardene A, et al. Abstract P4.1/12. NucleomaxX is an oral uridine supplement which may be given to prevent and revert mitochondrial toxicities. The effect of a single dose of NucleomaxX (36 g) on the pharmacokinetics of a single dose of zidovudine/lamivudine (300/150 mg) was studied in 8 HIV- subjects. Coadministration of NucleomaxX had no effect on the pharmacokinetics of zidovudine; however, lamivudine Cmax and Tmax were significantly higher, but there was no effect on AUC or half life. No adverse events were observed and the pharmacokinetics of zidovudine and lamivudine were consistent with historical data from HIV- subjects.
Report on 11th EACS, Madrid, October 2007 Different dose adjustments of immunosuppressants are necessary after initiating boosted or unboosted first protease inhibitor regimen post liver transplantation. Guaraldi G, Cocchi S, Ciaffi S, et al. Abstract P4.2/04. Plasma trough concentrations of ciclosporin, tacrolimus and rapamycin (sirolimus) were studied in 12 HIV+ subjects undergoing liver transplants. Following the addition of protease inhibitor therapy, the fold changes required to maintain therapeutic immunosuppressant concentrations were determined. After initiating a boosted protease inhibitor regimen (n=4), the mean fold decrease in immunosuppressant dose was 8.75 (range 6-14). The mean fold decrease required after initiating an unboosted protease inhibitor regimen (n=8) was 3 (range 2-4). No pharmacokinetic interaction between TMC125 and paroxetine in HIV-negative volunteers. Scholler-Gyure M, Kakuda TN, Bollen S, et al. Abstract P4.3/01 Coadministration of etravirine (125 mg twice daily, phase II formulation) and paroxetine (20 mg once daily) was investigated in 16 HIV- subjects. Etravirine increased paroxetine AUC, and Cmax by 3% and 6%, respectively, and decreased Cmin by 13%. AUC, Cmax and Cmin of etravirine increased by 1%, 5% and 7%, respectively. No dose adjustments are required when etravirine and paroxetine are coadministered. Effect of tipranavir/ritonavir treatment on the steady-state pharmacokinetics of bupropion in healthy volunteers. Lavrut T, Garraffo R, Ferrando S, et al. Abstract P4.3/03. The effect of tipranavir/ritonavir (500/200 mg twice daily) on the pharmacokinetics of bupropion (150 mg twice daily) was studied in 16 HIV- subjects. Coadministration decreased bupropion by ~50% with decreases (mean ± sd) observed for AUC (from 619 ± 248 to 337 ± 208 µg.h/L), Cmax (from 88.6 ± 38.5 to 51.4 ± 32.2 µg/L) and Cmin (from 27.0 ± 17.1 to 12.2 ± 8.4 µg/L). Exposure of the active metabolite (4-hydroxybupropion) decreased by ~25%. Increased ALT was observed in 6/16 subjects after 1 week of tipranavir/ritonavir, but returned to baseline by the end of the study in 5/6 subjects. Coadministration resulted in significant decreases in exposure to both bupropion and its active metabolite. Patients should be closely monitored for the therapeutic effect on depression. The pharmacokinetic interaction between atorvastatin and TMC278, a next generation NNRTI in HIV-negative volunteers. Van Heeswijk RPG, Hoetelmans, RMW, Aharchi F, et al. Abstract P4.3/04. Coadministration of the NNRTI TMC278 (150 mg once daily) and atorvastatin (40 mg once daily) was studied in 16 HIV- subjects. Atorvastatin had no significant effect on the pharmacokinetics of TMC278. Atorvastatin Cmax increased by 35% in the presence of TMC278, but there were no changes in AUC or Cmin. AUCs of the 2-OH and 4-OH metabolites of atorvastatin increased by 39% and 23% respectively. The AUC of total HMG-CoA reductase activity (as determined by the sum of atorvastatin, 2-OH and 4-OH atorvastatin) increased by 20%. No dosage adjustment is required when TMC278 and atorvastatin are coadministered.
Report on 11th EACS, Madrid, October 2007 Pharmacokinetics of the antifungal triazole posaconazole and the NRTI [sic] efavirenz when coadministered in healthy adult volunteers. Moton A, Ma L, Krishna G, et al. Abstract P4.3/05. Coadministration of efavirenz (400 mg once daily) and posaconazole (400 mg twice daily) was studied in HIV- subjects. Data from 10 subjects showed there was no effect on efavirenz AUC and a 13% increase in Cmax. However, data from 11 subjects showed that efavirenz decreased posaconazole exposure with AUC decreasing by 50% and Cmax by 45%. Based on these data, the authors suggest that concomitant use should be avoided unless the benefit outweighs the risk. Efavirenz-based versus nevirapine-based antiretroviral therapy among HIV-infected patients with tuberculosis and receiving rifampicin. Manosuthi W, Tansuphaswadikul S, Mankathitham W, et al. Abstract P7.3/29. When given with rifampicin, the recommendation is to increase efavirenz from 600 to 800 mg once daily. However, as the results of this safety and efficacy study show, this dose increase may not be necessary in all patients. A retrospective cohort study was conducted in 77 HIV/TB coinfected Thai subjects who received efavirenz 600 mg once daily and rifampicin. At 48 weeks, 78% of subjects achieved viral loads <50 copies/ml and CD% counts had risen to 253 cells/µL. No subjects discontinued therapy due to adverse events.
www.tendrleen.com Tend-R-Leen ®- a division of Domain, Inc. March, 2009 Pneumonia Prevention Pneumonia is a source of economic loss to cattle feeders, not VACCINATION PROGRAM: only in lost cattle, but also in terms of lost gains, treatment, These are only recommendations. Always consult your local medical expenses, and time spent doctoring sick steers. veterinari
ELECTRONICALLY REPRINTED FROM APRIL 14, 2006 HealthReference Pricing For DrugsBy Chuck Farkas and Preston HenskeIf an existing drug reduces cholesterol by ceutical industry as well, reaching $30 bil- investment trade-offs. lion to $35 billion in lost profits over theOne likely consequence will be a shift innext three to four years, according to analy-research toward diseases not currently