Current Issue : July - September Volume : 2015 Issue Number : 3 Articles : 7 Articles
Malaria caused by Plasmodium falciparum is responsible for approximately 80% of the incidence and 90% of deaths which occur\nin the World Health Organization (WHO) African region, with children and pregnant women having the highest incidence. P.\nfalciparumhas developed resistance, and therefore neweffective candidate antimalarial drugs need to be developed. Previous studies\nidentified 3,5-diaryl-2-aminopyridines as potential antimalarial drug candidates; therefore, derivatives of these compounds were\nsynthesized in order to improve their desired properties and pharmacokinetic (PK) properties of the derivatives were investigated\nin a mouse model which was dosed orally and intravenously. Collected blood samples were analyzed using liquid chromatography\ncoupled to mass spectrometer (LC-MS/MS). The mean peak plasma level of 1.9 ????M was obtained at 1 hour for compound 1 and\n3.3 ????Mat 0.5 hours for compound 2. A decline in concentration was observed with a half-life of 2.53 and 0.87 hours for compound\n1 in mice dosed orally and intravenously, respectively. For compound 2 a half-life of 2.96 and 0.68 hours was recorded. The\nbioavailability was 69% and 59.7% for compound 1 and compound 2, respectively....
Quetiapine is an atypical antipsychotic, used clinically in the treatment of schizophrenia, acute mania in bipolar disorders, and\nbipolar depression in adults. In this study, the effect of green tea extracts (GTE) on the pharmacokinetics of quetiapine (substrate\nof CYP3A4) was investigated in rats. Male Wistar albino rats received GTE (175mg/kg) or saline (control) by oral gavage for 7\ndays before a single intragastric administration of 25mg/kg quetiapine. Plasma concentrations of quetiapine were measured up to\n12 h after its administration by a validated ultraperformance liquid chromatography-tandem mass spectroscopy. Pretreatment with\nGTE produced significant reductions in the maximum plasma concentration and area under the curve of quetiapine by 45% and\n35%, respectively, compared to quetiapine alone. However, GTE did not produce significant change in elimination half-life and oral\nclearance of quetiapine. This study concluded that GTE may decrease the bioavailability of quetiapine when coadministered....
According to a survey from the National Health Insurance Research Database (NHIRD), Jia-Wei-Xiao-Yao-San (JWXYS) is the most\npopular Chinese medicine for cancer patients in Taiwan. 5-Fluorouracil (5-FU) is a general anticancer drug for the chemotherapy.\nTo investigate the herb-drug interaction of JWXYS on pharmacokinetics of 5-FU, a micro dialysis technique coupled with a high performance\nliquid chromatography system was used to monitor 5-FU in rat blood and brain. Rats were divided into four parallel\ngroups, one of which was treated with 5-FU (100mg/kg, i.v.) alone and the remaining three groups were pretreated with a different\ndose ofJWXYS (600, 1200, or 2400mg/kg/day for 5 consecutive days) followed by a combinationwith 5-FU.This study demonstrates\nthat 5-FU with JWXYS (600mg/kg/day or 1200mg/kg/day) has no significant effect on the pharmacokinetics of 5-FU in the blood\nand brain.However,JWXYS (2400mg/kg/day) coadministered with 5-FU extends the elimination half-life and increases the volume\nof distribution of 5-FU in the blood.The elimination half-life of 5-FU in the brain for the pretreatment group with 2400mg/kg/day\nof JWXYS is significantly longer than that for the group treated with 5-FU alone and also reduces the clearance.This study provides\npractical dosage information for clinical practice and proves the safety of 5-FU coadministered with JWXYS....
The concurrent use of drugs and herbal products is becoming increasingly prevalent over the last decade. Several herbal products\nhave been known to modulate cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp) which are recognized as representative\ndrug metabolizing enzymes and drug transporter, respectively.Thus, a summary of knowledge on the modulation of CYP and P-gp\nby commonly used herbs can provide robust fundamentals for optimizing CYP and/or P-gp substrate drug-based therapy. Herein,\nwe review ten popular medicinal and/or dietary herbs as perpetrators of CYP- and P-gp-mediated pharmacokinetic herb-drug\ninteractions.The main focus is placed on previous works on the ability of herbal extracts and their phytochemicals to modulate the\nexpression and function of CYP and P-gp in several in vitro and in vivo animal and human systems....
Objectives. TEACH (NCT00896051) was a randomized, open-label, two-arm Phase II trial to investigate the pharmacokinetic\ninteraction between etravirine and atazanavir/ritonavir and safety and efficacy in treatment-experienced, HIV-1-infected patients.\nMethods. After a two-week lead-in of two nucleoside reverse transcriptase inhibitors (NRTIs) and atazanavir/ritonavir 300/100mg,\n44 patients received etravirine 200mg bid with one NRTI, plus atazanavir/ritonavir 300/100mg or 400/100mg qd (n = 22 each\ngroup) over 48 weeks. Results. At steady-state etravirine with atazanavir/ritonavir 300/100mg qd or 400/100mg qd decreased\natazanavir Cmin by 18% and 9%, respectively, with no change in AUC24 h or Cmax versus atazanavir/ritonavir 300/100mg qd alone\n(Day -1). Etravirine AUC12 h was 24%higher and 16% lower with atazanavir/ritonavir 300/100 or 400/100mg qd, respectively, versus\nhistorical controls.At Week 48, no significant differences were seen between the atazanavir/ritonavir groups in discontinuations due\nto adverse events (9.1?ch group) and other safety parameters, the proportion of patientswith viral load <50 copies/mL (intent-totreat population, n (50.0%, atazanavir/ritonavir 300/100mg qd versus 45.5%, 400/100mg qd), and virologic\nfailures (31.8% versus 27.3%, resp.). Conclusions. Etravirine 200mg bid can be combined with atazanavir/ritonavir 300/100mg qd\nand an NRTI in HIV-1-infected, treatment-experienced patients without dose adjustment....
The purpose of this work was to study the effect of food on the drug release and floating behavior of gastro retentive dosage form. The objective was also to assess the role of biochemical property of drug in absorption. For this purpose ellagic acid was selected as acidic and monoammonium glycyrrhizin as basic drug. Floating tablet of both the drugs were prepared separately and evaluated for drug release and floating behavior in regular as well as bio relevant dissolution medium containing Ensure Plus®. Drug release of acidic drug increased from 90.5% to 96.7% in presence of food. This is due to increase in the pH of biological fluid causing greater ionization. Results of floating behavior showed that total floating time and floating lag time of formulation remains unaffected in presence of food. This may be due to presence of superdisintegrant crospovidone and channelizing agent mannitol in the formulation which facilitate faster entry of dissolution medium into the tablet leading to rapid dissolution. For basic drug, release showed no significant change in presence of food however floating behaviour was significantly affected. Drug release in regular dissolution medium was 98.15% while in presence of food it was 96.10%. For basic drug, increase in pH of dissolution medium did not alter ionization capacity of drug. Total floating time of formulation was unaffected in presence of food, however floating lag time increased considerably. This may be due to high viscosity of the dissolution medium and high tablet weight. Viscosity of dissolution medium, drug nature, volume of dissolution medium and excipients in the formulation play vital role in deciding drug release and floating properties....
Apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated effectiveness (versus placebo) for treatment of active psoriatic\narthritis in the psoriatic arthritis long-term assessment of clinical efficacy (PALACE) phase III clinical trial program.\nPharmacodynamic effects of apremilast on plasma biomarkers associated with inflammation were evaluated in a PALACE 1\nsubstudy. Of 504 patients randomized in PALACE 1, 150 (placebo: ???? = 51; apremilast 20mg BID: ???? = 51; apremilast 30mg\nBID: ???? = 48) provided peripheral blood plasma samples for analysis in a multiplexed cytometric bead array assay measuring\n47 proteins associated with systemic inflammatory immune responses. Association between biomarker levels and achievement of\n20% improvement from baseline in modified American College of Rheumatology (ACR20) response criteria was assessed by logistic\nregression. At Week 24, IL-8, TNF-n, IL-6, MIP-1n, MCP-1, and ferritin were significantly reduced from baseline with apremilast\n20mg BID or 30mg BID versus placebo. ACR20 response correlated with change in TNF-n level with both apremilast doses. At\nWeek 40, IL-17, IL-23, IL-6, and ferritin were significantly decreased and IL-10 and IL-1 receptor antagonists significantly increased\nwith apremilast 30mg BID versus placebo. In patients with active psoriatic arthritis, apremilast reduced circulating levels of Th1\nand Th17 proinflammatory mediators and increased anti-inflammatory mediators....
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