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排序方式: 共有518条查询结果,搜索用时 31 毫秒
71.
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Song I Borland J Min S Lou Y Chen S Patel P Wajima T Piscitelli SC 《Antimicrobial agents and chemotherapy》2011,55(7):3517-3521
Dolutegravir (DTG) is an unboosted, once-daily integrase inhibitor currently in phase 3 trials. Two studies evaluated the effects of etravirine (ETR) alone and in combination with ritonavir (RTV)-boosted protease inhibitors (PIs) on DTG pharmacokinetics (PK) in healthy subjects. DTG 50 mg every 24 h (q24h) was administered alone for 5 days in period 1, followed by combination with ETR at 200 mg q12h for 14 days in period 2 (study 1) or with ETR/lopinavir (LPV)/RTV at 200/400/100 mg q12h or ETR/darunavir (DRV)/RTV at 200/600/100 mg q12h for 14 days in period 2 (study 2). PK samples were collected on day 5 in period 1 and day 14 in period 2. All of the treatments were well tolerated. ETR significantly decreased exposures of DTG, with geometric mean ratios of 0.294 (90% confidence intervals, 0.257 to 0.337) for the area under the curve from time zero until the end of the dosage interval (AUC(0-τ)), 0.484 (0.433 to 0.542) for the observed maximum plasma concentration (C(max)), and 0.121 (0.093 to 0.157) for the plasma concentration at the end of the dosage interval (C(τ)). ETR combined with an RTV-boosted PI affected the exposure of DTG to a lesser degree: ETR/LPV/RTV treatment had no effect on the DTG plasma AUC(0-τ) and C(max), whereas the C(τ) increased by 28%. ETR/DRV/RTV modestly decreased the plasma DTG AUC(0-τ), C(max), and C(τ) by 25, 12, and 37%, respectively. Such effects of ETR/LPV/RTV and ETR/DRV/RTV are not considered clinically relevant. The combination of DTG and ETR alone should be avoided; however, DTG may be coadministered with ETR without a dosage adjustment if LPV/RTV or DRV/RTV is concurrently administered. 相似文献
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Shelton MJ Ford SL Borland J Lou Y Wire MB Min SS Xue ZG Yuen G 《Journal of acquired immune deficiency syndromes (1999)》2006,42(1):61-67
OBJECTIVES: To evaluate the drug interaction between fosamprenavir (FPV) and esomeprazole (ESO) after repeated doses in healthy adults. METHODS: Subjects received ESO 20 mg once daily (qd) for 7 days followed by either ESO 20 mg qd + FPV 1400 mg twice daily (bid) or ESO 20 mg qd + FPV 700 mg bid + ritonavir (RTV) 100 mg bid for 14 days in arms 1 and 2, respectively. After a 21- to 28-day washout, subjects received either FPV 1400 mg bid for 14 days (arm 1) or FPV 700 mg bid + RTV 100 mg bid for 14 days (arm 2). Pharmacokinetic sampling was conducted on the last day of each treatment. RESULTS: Simultaneous coadministration of ESO 20 mg qd with either FPV 1400 mg bid or FPV 700 mg bid + RTV 100 mg bid had no effect on steady-state amprenavir pharmacokinetics. The only effect on plasma ESO exposure was a 55% increase in area under the plasma concentration-time curve during a dosing interval, tau[AUC0-tau], after coadministration of ESO 20 mg qd with FPV 1400 mg bid. CONCLUSIONS: FPV 1400 mg bid or FPV 700 mg bid + RTV 100 mg bid may be coadministered simultaneously with ESO without dose adjustment. However, the impact of staggered administration of proton pump inhibitors (PPI) on plasma amprenavir exposure is unknown at present. 相似文献
75.
Dahlke MH Loi R Warren A Holz L Popp FC Weiss DJ Piso P Bowen DG McCaughan GW Schlitt HJ Bertolino P 《Journal of hepatology》2006,44(2):334-341
BACKGROUND/AIMS: The role of adult bone marrow-derived cells (BMC) in hepatic regeneration is controversial. Both transdifferentiation of BMC as well as fusion with hepatocytes have been suggested in toxin-based and genetic selection models. METHODS: We have developed a transgenic mouse model of immune-mediated hepatitis to clarify the role of BMC in liver regeneration following injury mediated by T cells. RESULTS: Repeated adoptive transfer of transgenic T cells into bone marrow chimeras resulted in multiple waves of hepatitis. Hepatocytes derived from donor bone marrow were identified using a self-protein that does not interfere with hepatocyte function and proliferation in recipient animals. Some cells contained one recipient nucleus and another independent donor bone marrow-derived nucleus, suggesting that cellular fusion plays some role in liver repair after immune hepatitis. However, despite pronounced infiltration by myeloid cells, the frequency of fusion was extremely low. CONCLUSIONS: This study provides a unique, clinically relevant model in which fusion hepatocytes can be purified and characterized by the expression of donor MHC antigen. It demonstrates that although fusion between BMC and hepatocytes occurs under conditions of inflammation that correspond to human disease, its frequency needs to be increased to be of any therapeutic value. 相似文献
76.
Cannas A Solla P Floris G Tacconi P Loi D Marcia E Marrosu MG 《Progress in neuro-psychopharmacology & biological psychiatry》2006,30(8):1539-1541
Neuropsychological and psychopathological modifications induced by dopaminergic drugs in patients with Parkinson's disease (PD) are invariably not taken into sufficient consideration by the neurologist. Among the former, modifications of sexual urges and behaviours are of particular importance with regard to severity and variety of clinical pictures. Although rare, such modifications may assume the connotations of an aberrant sexual behaviour with criminal implications, in line with a diagnosis of paraphilia. The authors report the case of a 51-year-old male PD patient who, after a few years of dopaminergic treatment with pergolide, developed a paraphilic disorder, consistent with DSM-IV TR diagnosis of frotteurism, and delusional jealousy. The patient presented mild motor impairment and lack of or negligible cognitive deterioration, thus providing evidence that these disorders are not typical of advanced PD. Pergolide was reduced and quetiapine, an atypical neuroleptic, was introduced with subsequent subsiding of the paraphilic disorder and improvement of delusional jealousy. 相似文献
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Carai MA Fantini N Loi B Colombo G Gessa GL Riva A Bombardelli E Morazzoni P 《The British journal of nutrition》2011,106(5):762-768
Previous lines of experimental evidence have suggested that Phaseolus vulgaris extracts reduce food intake, body weight, lipid accumulation, hedonic properties of food, carbohydrate absorption and metabolism, and glycaemia in rats. The present study was designed to assess the effect of multiple cycles of repeated treatments with a standardised P. vulgaris dry extract on daily food intake and body weight in genetically obese Zucker fa/fa rats (Expt 1). Additionally, the study tested the effect of acute treatment with P. vulgaris dry extract on postprandial glycaemia in Zucker fa/fa rats (Expt 2). In Expt 1, P. vulgaris dry extract was administered daily, at doses of 50 and 500 mg/kg, in three 5 d treatment periods followed by three 20 d off-treatment periods. Administration of P. vulgaris dry extract resulted in dose-dependent decreases in daily food intake and body weight in each treatment phase. Reductions in food intake were of comparable magnitude in each treatment phase. In Expt 2, food-deprived rats were acutely treated with 50 and 500 mg P. vulgaris dry extract per kg immediately before access to a fixed amount of a starch-enriched chow. Treatment with P. vulgaris dry extract resulted in a dose-dependent suppression of glycaemia. These results extend previous data on the anorectic and hypoglycaemic effects of the P. vulgaris dry extract to a validated animal model of obesity. Together with data published previously in the literature, these results strengthen the hypothesis that potentially effective, novel pharmacotherapies for obesity and related disorders may originate from extracts and derivatives of P. vulgaris. 相似文献