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971.
The steady-state disposition of chlorzoxazone (CZX) and its hydroxylated metabolite 6-hydroxychlorzoxazone (HCZX) was determined in a single-pass isolated perfused rat liver (IPRL) model using constant CZX concentrations of 10-200 microM. The concentrations of CZX, HCZX, and/or HCZX glucuronide in the perfusate, bile, and liver tissues were measured and kinetic parameters calculated. Upon an increase in CZX inlet concentrations from 10 to 200 microM, its extraction ratio sharply declined from 0.681 to 0.087. This was associated with a saturable formation of HCZX, which was rapidly and completely metabolized to its glucuronide conjugate. Whereas the biliary excretion of CZX was negligible, that of HCZX was substantial (up to 40% of the generated metabolite). Overall, 79-93% of the CZX dose (10-200 microM) was recovered in our model as CZX and HCZX. Additionally, HCZX accounted for 56% (200 microM) to 71% (10 microM) of the extracted CZX dose. Further, a preliminary study using the preformed HCZX showed a complete (100%) recovery of the metabolite as its conjugate. Therefore, the unrecovered portion of CZX dose in our study (7-21% of the administered dose or 29-44% of the extracted dose at inlet CZX concentrations of 10-200 microM) is most likely due to parallel metabolism of CZX to other metabolites. 相似文献
972.
973.
Mehdizadeh A Ghahremani MH Rouini MR Toliyat T 《Acta pharmaceutica (Zagreb, Croatia)》2006,56(2):219-229
Drug-in-adhesive patches (DIAPs) of fentanyl were formulated using various pressure sensitive adhesives (PSAs) and various chemical permeation enhancers (CPEs). The effects of PSAs and CPEs on skin permeation of fentanyl from DIAPs were evaluated using modified jacketed Franz diffusion cells fitted with excised rat abdominal skin. It was demonstrated that the permeation rate or steady state flux (J(ss)) of the drug through the excised rat skin was dependent on the viscosity and type of acrylic PSA as well as the type of CPE. Among different acrylic PSAs, Duro-Tak 2054 and Duro-Tak 2516 showed the highest J(ss) of 1.95 microg cm(-2) h(-1) and the lowest J(ss) of 1.43 microg cm(-2) h(-1), respectively. Among the various CPEs used, propylene glycol and polyethylene glycol 400 showed 1.61 and 1.18, the highest and the lowest enhancement ratios (ER) of the skin permeation of fentanyl, respectively. Oleic acid and cetyl alcohol moderately increased the skin permeation of fentanyl. It was also shown that increasing the concentration of CPE led to reduction in the adhesion property of PSA as measured by the 180 degrees peeling strength test. Moreover, it was found that the permeation rate increased as the fentanyl loading increased from 1 to 3%. The skin permeation rate of fentanyl did not increase significantly beyond 3% drug loading. It was concluded that propylene glycol as a CPE and cosolvent in 10% (m/m) with 3% fentanyl loading in Duro-Tak 2054 showed an effective monolithic DIAP for the development of a transdermal therapeutic system for fentanyl. 相似文献
974.
Zarei R Azimi R Moghimi S Abdollahi A Amini H Eslami Y Fakhraii G 《Journal of cataract and refractive surgery》2006,32(11):1921-1925
PURPOSE: To evaluate the effect of intraocular infusion of dalteparin, a low-molecular-weight heparin (LMWH) administered in the infusion fluid to prevent early postoperative fibrin formation in combined phacoemulsification-trabeculectomy surgery (phacotrabeculectomy). SETTING: Farabi Eye Hospital, Tehran, Iran. METHODS: Standard combined phacotrabeculectomy was performed prospectively in a masked fashion in 60 eyes; 35 eyes received 5 IU/mL LMWH in the infusate and 25 eyes served as controls. Masked postoperative examinations assessed visual acuity, intraocular pressure (IOP), anterior chamber cell and flare, and fibrin formation with slitlamp examinations 1, 3, 7, 30, and 90 days after surgery. RESULTS: The rate of intraocular fibrin/membrane formation was significantly lower in the LMWH group than in the control group at each follow-up (P<.001, Student t test) . The amount of IOP was lower in LMWH group at each follow up (P<.01, Student t test). Final visual acuity was better in LMWH group (P = .03, Student t test). The frequency of synechia formation was lower in the LMWH group on day 90 (P = .002, chi-square test). CONCLUSIONS: Infusion of dalteparin, a LMWH, may be an effective inhibitor of postoperative fibrin formation in phacotrabeculectomy surgery. It may reduce the frequency of synechia formation and improve visual acuity. It may not be associated with increased risk for intraoperative or postoperative complications at the tested dose. This drug may be a useful adjunct in combined surgery. 相似文献
975.
Mehvar R 《American journal of pharmaceutical education》2006,70(5):96
Population pharmacokinetic data, adjusted for patient characteristics, are recommended for the design of initial dosage regimens of some therapeutically monitored drugs in patients for whom patient-specific data are not available. However, despite widespread use by clinicians such as pharmacists, a clear understanding of the principles of population pharmacokinetics, including data collection and analysis and its limitations, is often lacking. This article describes the 2 main methods of obtaining population kinetic data, namely the two-stage method and nonlinear mixed effect model, and their applications to the pharmacokinetic-based design of dosage regimens. Additionally, some numerical examples are provided to assist the reader in understanding the material. The author uses these tools in a pharmacokinetics course taught to PharmD students. 相似文献
976.
Several studies indicate that central serotonergic neurons have important role in morphine analgesia and tolerance. The aim of this study was to investigate possible role of 5-HT(1A) and 5-HT(2) receptors in dorsal and median raphe nucleus on development of tolerance to analgesic effect of morphine using hot plate test. Chronic injection of 5-HT(1A) receptor agonist 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino]tetralin) (2, 4 and 8 mug/rat/day) to dorsal raphe nucleus (DRN) delayed tolerance to morphine analgesia, whereas injection of the same doses of 8-OH-DPAT to the median raphe nucleus (MRN) did not alter tolerance to morphine. In addition, chronic administration of ketanserin (1.5, 3 and 6 mug/rat/day), as a 5-HT(2) receptors antagonist, in DRN and MRN did not produce any significant effect. We conclude that 5-HT(1A) receptors of DRN are involved in tolerance to antinociceptive effect of morphine. However, the exact mechanism of interaction between serotonergic and opioidergic systems is not clear and remains to be elucidated. 相似文献
977.
A. Strother I. M. Fraser Reza Allahyari B. E. Tilton 《Bulletin of the World Health Organization》1981,59(3):413-425
Some of the most effective antimalarial agents are derivatives of 8-aminoquinoline. The metabolic products of many of these compounds appear to be toxic to the erythrocytes of certain human subjects, especially those deficient in glucose-6-phosphate dehydrogenase. Although a number of studies have been conducted over many years, the metabolism of most of these compounds has not been determined. These studies are reviewed. 相似文献
978.
A case of enteric duplication is reported in which preoperative pertechnetate 99mTc scanning demonstrated localized uptake in the region of the anatomic abnormality. This test is recommended for use in the evaluation of lower gastrointestinal bleeding in infants and children. 相似文献
979.
PURPOSE: To describe four patients with optic nerve sheath meningioma in whom visual improvement began to occur even before completion of a standard course of radiation therapy. DESIGN: Retrospective case review. METHODS: A review was conducted of 35 patients who received stereotactic three-dimensional conformal radiotherapy for optic nerve sheath meningioma from 1990 to 2005. RESULTS: Four patients with radiographic confirmation of optic nerve sheath meningioma were identified who had neuro-ophthalmologic assessment, which included perimetry, either while radiation treatment was underway or immediately afterwards. All of the patients showed improvement in visual acuity and visual fields. CONCLUSION: A rapid response to radiation therapy may occur in some patients with optic nerve sheath meningioma. In such patients, it may be possible to customize the radiation dose by assessing of visual function during the course of therapy. 相似文献
980.
PURPOSE: To investigate whether central corneal thickness (CCT) is affected in patients with Weill-Marchesani syndrome (WMS) and to focus on its clinical significance. DESIGN: Case-control study. METHODS: Complete ocular examination was performed in case and control groups, and then the lowest reading of ten pachymetry measurements of the central cornea was taken as CCT. RESULTS: All participants, case and controls, were female and age matched (P = .7). The mean of central corneal thickness in twelve eyes of six patients with WMS was thicker (631.5 +/- 25.9 microns) than 40 eyes of 20 normal persons (535.8 +/- 25.9 microns) in the control group (P < .0001). CONCLUSIONS: Increased CCT seems to be a previously unrecognized aspect of WMS. This may lead to overestimation of intraocular pressure by applanation tonometers. Therefore, unusually thick CCT should be considered in interpreting the Goldmann tonometric reading in diagnosis and management of glaucoma in this rare syndrome. 相似文献