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无环鸟苷亲脂性前体药物脂质体的制备及体外抗病毒活性(英文) 总被引:2,自引:0,他引:2
本文通过将无环鸟苷(acyclovir,简称ACV)2’位羟基分别与月桂酰氯或棕榈酰氯进行酯化反应,制得亲脂性前体药物无环鸟苷月桂酸酯和无环鸟苷棕榈酸酯(分别简称为C12-ACV和C16-ACV),使脂质体包封率从ACV的29.9%提高到C12-ACV的95.6%和C16-ACV的97.1%;漏泄实验表明在4℃透析60h后,一半以上的ACV从脂质体中漏泄,而C12-ACV和C16-ACV的滞留率分别为70%和80%;体外抗疱疹病毒的试验中,在最低试验浓度0.044μmol/L时,ACV不显示抗病毒活性,而C16-ACV脂质体抑制细胞病变率达75%,说明前体药物通过与脂质体脂膜的结合增加了药物的进入细胞能力,从而提高了ACV的抗病毒能力。 相似文献
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A survey was conducted to ascertain general medical practitioners' (GPs') attitudes to community pharmacists' use of patient medication records (PMRs) and to assess whether GPs envisage a role for family health service authorities (FHSAs) in maintaining records of patients' data. The survey questionnaire was sent by post to all 1,257 GPs in contract with Avon and Devon FHSAs. A total of 811 questionnaires was returned, an overall response rate of 64.5 per cent. A majority (59 per cent) of GPs considered that community pharmacists should keep patient medication records and there was strong support for pharmacists holding PMRs for the elderly and confused, and also for patients with diabetes, asthma, epilepsy, and those patients who had experienced major adverse drug reactions or allergies. Some GPs, however, remained unconvinced of the usefulness of a pharmacy PMR. Seventy four per cent of respondents considered that patients should keep their own medication records. In contrast, only 4 per cent were in agreement with patient medication data being stored by FHSAs. The community pharmacist's role in maintaining PMRs received less support from doctors in dispensing practices than from their non-dispensing counterparts. Some 80 per cent of respondents were in favour of pharmacists providing PMR system-generated patient information leaflets with dispensed medicines. Most GPs considered that such leaflets had a positive effect on patient compliance. Recently registered GPs were found to be more supportive than their older colleagues of community pharmacists recording patients' clinical conditions and providing information leaflets. 相似文献
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S. G. WOOLFREY J. HEGBRANT H. THYSELL P. A. FOX D. W. LENDREM G. F. LOCKWOOD K. LASHER J. ROGERS D. GREENSLADE 《The Journal of pharmacy and pharmacology》1995,47(8):651-655
This study was designed to test a proposed dose modification for intravenous milrinone in congestive heart failure patients (CHF, NYHA I-II) with either moderate or severe renal impairment. All the patients were administered an intravenous loading dose of drug at 50 μg kg-1 over 10 min. This was followed by an 18 h maintenance infusion of milrinone at 0·45 or 0·35 μg kg?1 min?1 for the moderate (chromium-EDTA clearance of 31–75 mL min?1, n = 10) and severe renally impaired subjects (chromium-EDTA of clearance 10–30 mL min?1, n = 11), respectively. Plasma and urine samples were collected for up to 34 h and analysed for parent drug by validated HPLC methods. The mean (± s.d.) steady-state plasma concentrations of milrinone were within the therapeutic range (100–300 ng mL?1) for both groups, with values of 239 ± 71 ng mL?1 and 269 ± 32 ng mL?1 for the moderate and severe patients, respectively. No statistical differences were observed between the steady-state values for the two groups. With the exception of two patients per group, individual steady-state levels were also within the therapeutic range. Those outside the nominal range showed steady-state levels, ranging between 308 and 353 ng mL?1, that were not associated with any serious adverse events. As predicted for this highly renally cleared drug, there were differences (P < 0·001) in the total plasma clearance (CLP), renal clearance (CLr), and plasma terminal half-life (t1/2) of drug, with values in the severe group being 44% lower, 75% lower, and about 134% longer respectively, when compared with the moderate group. High (correlation coefficient > 0·8) and significant correlations (P < 0·001) were observed between CLP and CLr and the degree of renal impairment (chromium-EDTA clearance). The apparent volume of distribution was approximately 40% higher (P < 0·01) in the severe group compared with that for the moderate group (moderates were 0·443 ± 0·155 L kg?1). This volume difference suggests a decrease in the plasma protein-binding of milrinone because of the renal disease. The fraction of drug excreted in the urine was 0·705 ± 0·100 for the moderate group and 0·320 ± 0·089 for the severe group (P < 0·001). These results may suggest an increase in non-renal clearance of the compound, representing a partial compensation mechanism for the reduced renal function. In conclusion, this study has confirmed that the current dose reductions recommended for the use of intravenous milrinone in CHF patients with impaired renal function will yield plasma concentrations of the drug within the therapeutic range. 相似文献
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There has been a recent renewal of interest in the use of monoamineoxidase inhibitors in psychiatry. The concurrent administrationof anaesthetic agents, particularly narcotic analgesics, isoften a cause for concern. Although many monoamine oxidase inhibitordruginteractions have been reported, in practice it is only theinteraction with pethidine which has led to fatalities. Whatis not appreciated is that the monoamine oxidase inhibitorpethidineinteraction has two distinct forms"excitatory" and "depressive".It is this lack of appreciation that has led to much confusionwhen dealing with patients taking monoamine oxidase inhibitors. 相似文献
10.
A multiple-pathway model for the diffusion of drugs in skin 总被引:1,自引:0,他引:1
A mathematical model for the diffusion of drugs in skin is presented.The penetration of the drug by both transcellular and intercellularpathways, as well as its interchange between these pathways,is considered. A pharmacologically motivated asymptotic limitis identified and analysed to obtain, in particular, an analyticalexpression for the flux of drug to the blood at steady state.Relevant model data is discussed, and some numerical resultsare also presented. 相似文献