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41.
Pharmaceutical Research - 相似文献
42.
Green Philip G. Hinz Robert S. Kim Aeri Szoka Francis C. Guy Richard H. 《Pharmaceutical research》1991,8(9):1121-1127
The iontophoresis of eight tripeptides, of the general structure alanine–X–alanine, has been measured across hairless mouse skin in vitro. The peptides were blocked (a) at the carboxyl terminus using the mixed anhydride reaction with t-butylamine and (b) at the amino terminus by acetylation with 14C-acetic anhydride. The nature of the central residue (X) was varied by selecting one of five neutral amino acids, two negatively chargeable moieties (aspartic and glutamic acids), and a positively chargeable species (histidine). Constant current iontophoresis at 0.36 mA/cm2, using Ag/AgCl electrodes, was performed for 24 hr in diffusion cells, which allowed both anode and cathode to be situated on the same (epidermal) side of a single piece of skin. Due to a combination of osmotic and electroosmotic forces, the anodal iontophoretic flux of neutral peptides was significantly greater than passive transport. Steady-state fluxes were not achieved, however, suggesting that time-dependent changes in the properties of the skin barrier may be occurring. Limited, further experiments confirmed that, on a 24-hr time scale, these changes were not fully reversible. The cathodal delivery of anionic permeants was well controlled at a steady and highly enhanced rate by the current flow. This behavior closely paralleled earlier work using simple negatively charged amino acids and N-acetylated amino acid derivatives. It appears that the normalized iontophoretic flux of these anionic species is independent of lipophilicity but may be inversely related to molecular weight. The positively charged peptide, Ac–Ala–His–Ala–NH(But), showed greater anodal iontophoretic enhancement when delivered from a donor solution at pH 4.0 than from a solution at pH 7.4. This was consistent with (a) the corresponding behavior of histidine alone and (b) the existence of a pK
a for these compounds at 6. Steady-state delivery was not achieved, although the levels of enhancement, especially at pH 4, were the largest observed. A preliminary investigation of tripeptide stability to either (i) electrolysis in the donor compartment or (ii) cutaneous metabolism revealed very little degradation under the conditions of the experiment. Overall, this research supports the principle of enhanced peptide delivery across the skin by iontophoresis and indicates a number of areas (e.g., mechanism and extent of current-induced changes in skin barrier function, molecular size dependence, pathways of current flow) on which further work should be focused. 相似文献
43.
Kikkoji Toshihiro Gumbleton Mark Higo Naruhito Guy Richard H. Benet Leslie Z. 《Pharmaceutical research》1991,8(10):1231-1237
The percutaneous penetration kinetics of the antianginal, nitroglycerin (GTN), and its primary metabolites, 1,2- and 1,3-glyceryl dinitrate (1,2- and 1,3-GDN), were evaluated in vitro, using full-thickness hairless mouse skin. GTN and the 1,2- and 1,3-GDNs were applied (a) in aqueous solution as pH 7.4 phosphate-buffered saline (PBS) and (b) incorporated into lipophilic ointment formulations. The cutaneous transformation of GTN to its dinitrate metabolites was detected, but no interconversion between 1,2-GDN and 1,3-GDN was observed. Following application of the nitrates in PBS solution, all three compounds exhibited steady-state transport kinetics. The steady-state flux of GTN (8.9 ± 1.5 nmol cm–2 hr–1) was significantly greater (P < 0.05) than those of 1,2-GDN (0.81 ± 0.54 nmol cm–2 hr–1) and 1,3-GDN (0.72 ± 0.20 nmol cm–2 hr–1). The corresponding permeability coefficient () for GTN (20 ± 3 × 10–3 cm hr–1) was significantly larger than the corresponding values for 1,2-GDN (1.4 ± 0.9 × 10–3 cm hr–1) and 1,3-GDN (1.2 ± 0.4 × 10–3 cm hr–1), which were statistically indistinguishable (P > 0.05). Further analysis of the transport data showed that the differences between GTN and the GDNs could be explained by the relative stratum corneum/water partition coefficient (K
s) values of the compounds. The apparent partition parameters, defined as = K
s · h [where h is the diffusion path length through stratum corneum (SC)] were 19.8 ± 2.5 × 10–2 cm for GTN and 1.91 ± 1.07 × 10–2 and 1.81 ± 0.91 × 10–2 cm for 1,2- and 1,3-GDN, respectively. However, when the nitrates were administered in an ointment base, the apparent partition parameter (') and permeability coefficient (') of GTN markedly decreased, to 2.51 ± 0.75 × 10–2 cm and 1.6 ± 0.3 × 10–3 cm hr–1, respectively. In contrast, the ' and ' results for 1,2- and 1,3-GDN were not significantly different (P > 0.05) from the corresponding and values, which were measured following dosing as aqueous solutions. As a result, the steady-state fluxes of all three nitrates from the ointment formulation were comparable (GTN, 154 ± 28 nmol cm–2 hr–1; 1,2-GDN, 162 ± 22 nmol cm–2 hr–1; 1,3-GDN, 162 ± 34 nmol cm–2 hr–1). It follows that the dinitrates can be as efficiently delivered across the skin as GTN when a suitable formulation is employed. This finding may support transdermal therapy using 1,2- or 1,3-GDN if, indeed, they are found to be pharmacologically effective. 相似文献
44.
F. A. Campbell S. M. Yentis D. W. Fear B. Bissonnette 《Journal canadien d'anesthésie》1992,39(7):661-664
The analgesic efficacy and safety of a single caudal injection of a bupivacaine-fentanyl mixture was investigated in this prospective, controlled, triple-blinded study of 34 children, aged 1-11 yr and of ASA physical status I-II undergoing urological surgery. After induction of anaesthesia and before surgery, the children were randomly assigned to receive a caudal injection of 1.0 ml.kg-1 bupivacaine 0.125% with epinephrine 1:400,000 and either fentanyl 1.0 microgram.kg-1 in 1.0 ml of normal saline or 1.0 ml of normal saline. After completion of surgery, patients were assessed in the recovery room for six hours from the time of the caudal injection and for a further 18 hr on the ward. While in the recovery room arterial oxygen saturation and respiratory rate were monitored continuously and recorded hourly together with end-tidal carbon dioxide, pain and sedation scores. Other complications were also recorded. While on the ward, pain and sedation scores, respiratory rate and side effects were recorded every two hours. Postoperative analgesia was provided by intravenous morphine. Analgesic requirements were recorded for the 24-hr study period. Pain and sedation scores did not differ between groups. Respiratory depression or hypoxia did not occur. The incidences of other side effects did not differ. There were no differences in the numbers of patients requiring morphine within eight hours, the time to first morphine administration or the total morphine requirements. We conclude that a single caudal injection of a bupivacaine-fentanyl mixture with epinephrine administered prior to surgery, while safe, offers no advantage over an injection of bupivacaine 0.125% with epinephrine for paediatric urological surgery. 相似文献
45.
Martin J. White Edward J. Berghausen Stephen W. Dumont Kentaro Tsueda Julia A. Schroeder Robert L. Vogel Michael F. Heine Kou Chu Huang 《Journal canadien d'anesthésie》1992,39(6):576-582
Respiratory effects, nausea, somnolence, and pruritus were compared during a 48-hr period of continuous epidural morphine (n = 34) and fentanyl (n = 32) infusion in 66 patients following elective total replacement of the hip or knee joint. Respiratory effects were assessed by PaCO2. Side effects were assessed by visual analogue scale and considered to be present when the score was above 30. Assessment was made at preoperative visits then 3, 6, 12, 24, 36, and 48 hr after the epidural injection. The bolus dose and subsequent infusion rate were 3,900 +/- 1,300 micrograms and 427 +/- 213 micrograms.hr-1 for morphine, and 85 +/- 46 micrograms and 56 +/- 27 micrograms.hr-1 for fentanyl. Pain relief was similar in both groups. In the morphine group, PaCO2 elevation and nausea occurred over a period of more than 12 hr (P less than 0.05). In the fentanyl group, there was no PaCO2 change, and nausea was confined to the first few hours. Nausea was more severe (P less than 0.01 at six hours and more frequent (24 hr cumulative incidence, 53 vs 28%, P less than 0.05) in the morphine group. Somnolence was prominent within several hours in two-thirds of patients in both groups. Somnolence continued to decline thereafter in the morphine group, but it was demonstrable in approximately half of the patients throughout the second day in the fentanyl group. The incidence was higher in the fentanyl group at the 48th hr (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
46.
Epidural infusions of fentanyl, in a 10 micrograms.ml-1 concentration, combined with bupivacaine 0.1% were compared with epidural infusions of fentanyl alone for postoperative analgesia following abdominal or thoracic surgery. There were no detectable differences between the two groups in analgesia (mean visual analogue scale pain scores ranging between 15-35 mm), average infusion rates of 7-9 ml.hr-1, and serum fentanyl concentrations which reached 1-2 ng.ml-1. There was no difference in postoperative pulmonary function (pH, PaCO2, SaO2), or bowel function (time to flatus or po fluids). The incidence of side-effects including somnolence, nausea and vomiting, pruritus and postural hypotension was also similar. Of the patients receiving fentanyl and bupivacaine 0.1%, three developed a transient unilateral sensory loss to pinprick and ice, and two of these patients had unilateral leg weakness equal to a Bromage 1 score. The addition of bupivacaine 0.1% does not improve epidural infusions of fentanyl using a 10 micrograms.ml-1 concentration following abdominal or thoracic surgery. 相似文献
47.
A term parturient with documented platelet dysfunction presented to the case room for induction of labour. Since this bleeding
abnormality contraindicated the use of lumbar epidural analgesia (LEA), we elected to use an iv fentanyl patientcontrolled
analgesia (PCA) technique for pain relief during labour. The patient received a 50 μg fentanyl loading dose after which 20
μg boluses of fentanyl were self-administered every three minutes as required. The patient received a total of 400 μg of fentanyl
over the 3 1/2 hr of active labour. Mother and neonate tolerated the fentanyl without sequelae. If facilities to monitor the
neonate and mother are present, this method of analgesia is useful in those patients where LEA is contraindicated.
Au terme d’une grossesse, une patiente porteuse d’une dysfonction plaquettaire devait avoir une induction de travail au bloc
obstétrical. Ecartant l’usage d’une epidurale à cause des risques de saignement, nous avons employé du fentanyl en autoanalgésie
(PCA) pour soulager les douleurs du travail. Après une dose initiate de50 μg, la patiente s’injectait des doses de 20 μg de
fentanyl iv aux 3 minutes prn. Elle utilisa un total de 400 μg de fentanyl au cours des 3,5 heures que dura le travail. La
mère et le nouveau-né tolérèrent fort bien ce mode d’analgésie. L’autoanalgésie offre done une alternative au bloc épidural
lorsque ce dernier est contre-indiqué toutefois, nous recommandons de monitorer la mére et le nouveau-né pendant quelques
heures. 相似文献
48.
Tussive effect of a fentanyl bolus 总被引:10,自引:0,他引:10
Wee Thuan Phua Boon Teck Teh Winston Jong Tat Leang Lee William A. Tweed 《Journal canadien d'anesthésie》1991,38(3):330-334
The aim of this study was to investigate the incidence of pre-induction coughing, after an iv bolus of fentanyl. The study sample was 250 ASA physical status I-II patients, scheduled for various elective surgical procedures. The first 100 were randomly allocated to receive 1.5 micrograms.kg-1 fentanyl via a peripheral venous cannula (Group 1), or an equivalent volume of saline (Group 2). Twenty-eight per cent of patients who received fentanyl, but none given saline, coughed within one minute (P less than 0.0001). The second 150 patients were then randomly assigned to three equal pretreatment groups. Group 3 received 0.01 mg.kg-1 atropine iv one minute before fentanyl. Groups 4 and 5 received 0.2 mg.kg-1 morphine im, and 7.5 mg midazolam po, respectively, one hour before fentanyl. Thirty per cent of patients in Group 3, 6% in Group 4, and 40% in Group 5, had a cough response to fentanyl. Fentanyl, when given through a peripheral cannula, provoked cough in a considerable proportion of patients. This was not altered by premedication with atropine or midazolam, but was reduced after morphine (P less than 0.01). Coughing upon induction of anaesthesia is undesirable in some patients, and stimulation of cough by fentanyl in unpremedicated patients may be of clinical importance. 相似文献
49.
目的 了解机械通气患儿以小剂量芬太尼持续静脉滴注的作用。 方法 观察用药前后呼吸顺应性 (Cdyn)、气道阻力 (Raw)及呼气末二氧化碳分压 (PetCO2 )的变化。 结果 1个月~ 3岁患儿用药前后Raw及PetCO2 明显下降 ,肺部感染患儿指标变化显著大于非感染患儿 ,Cdyn用药前后均未发现显著差异。 结论 提示机械通气中用小剂量芬太尼可以减轻人机对抗 ,降低气道压 ,改善肺气体交换及肺功能 ,有利于患儿顺利地渡过危险期 相似文献
50.
咪喹莫特脂质体与乳膏体外经皮扩散行为的比较 总被引:4,自引:1,他引:4
采用中和法制备咪喹莫特脂质体,研究了其体外经皮扩散行为并与咪喹莫特乳膏进行比较。制得的脂质体平均粒径为855nm,跨距为1.65,能经皮缓慢扩散,皮层的局部贮药量比之乳膏有增加,可减少药物全身吸收。 相似文献