共查询到20条相似文献,搜索用时 31 毫秒
1.
John Dewar 《British medical journal》1882,2(1131):414-415
2.
Vaddady PK Mehrotra N Zhang X Yates CR Moore BM Meibohm B 《Biopharmaceutics & drug disposition》2011,32(2):89-98
Hemorrhagic shock involves loss of a substantial portion of circulating blood volume leading to diminished cardiac output and oxygen delivery to peripheral tissues. In situations where an immediate resuscitation cannot be provided, pharmacotherapy with a novel combination of Δ9‐tetrahydro‐cannabinol (THC) and celecoxib (CEL) is currently investigated as an alternative strategy to prevent organ damage. In the present study, 28 Yorkshire × Landrace pigs were used to study the pharmacokinetics of THC and CEL in an established porcine model of hemorrhagic shock. Pigs in hemorrhagic shock received 0.5, 1 or 4 mg/kg THC and 2 mg/kg CEL, while normotensive pigs received 1 mg/kg THC and 2 mg/kg CEL by intravenous injection. THC and CEL plasma concentrations were simultaneously determined by LC‐MS/MS. Pharmacokinetic parameters and their between animal variability were obtained using standard non‐compartmental analysis as well as a compartmental analysis using nonlinear mixed effects modeling. The concentration–time profiles of THC and CEL followed a multi‐exponential decline and their pharmacokinetics were similar in hemorrhagic shock and normotensive conditions, despite the substantial change in hemodynamics in the animals with shock. This interesting finding might be due to the pharmacologic effect of the THC/CEL combination, which is intended to maintain adequate perfusion of vital organs in shock. Overall, this study established THC and CEL pharmacokinetics in a porcine shock model and provides the basis for dose selection in further studies of THC and CEL in this indication. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
3.
Jan Peter Yska Guus W.G. Essink Adriaan A. van Sorge Frank H. Bosch Gert Lankhaar 《Pharmacy World & Science》2000,22(2):67-71
Purpose: A threeway crossover study with seven healthy male volunteers was conducted to determine the relative bioavailability of phenobarbital after single dose administration of 100 mg of phenobarbital as oral solution in Myvacet 908, and as a suspension, compared with a 100 mg phenobarbital tablet. Materials and methods: At 4week intervals each subject received the solution in Myvacet 908, the suspension and the tablet in randomized order. Blood samples were collected for 48 h after each dose for analysis of phenobarbital. From the individual serum concentrationversustime curves C
maxand T
max were determined and AUC048 was calculated. Results: All three oral dosage forms of phenobarbital are bioequivalent. No significant diffences in T
maxwere observed. Conclusion: The oral solution in Myvacet 908, and the suspension of phenobarbital proved to be bioequivalent to a tablet. 相似文献
4.
Mehruba Anwar Amelia Kasper Alaina R. Steck Joshua G. Schier 《Journal of medical toxicology》2017,13(2):173-179
Introduction
Bongkrekic acid (BA) has a unique mechanism of toxicity among the mitochondrial toxins: it inhibits adenine nucleotide translocase (ANT) rather than the electron transport chain. Bongkrekic acid is produced by the bacterium Burkholderia gladioli pathovar cocovenenans (B. cocovenenans) which has been implicated in outbreaks of food-borne illness involving coconut- and corn-based products in Indonesia and China. Our objective was to summarize what is known about the epidemiology, exposure sources, toxicokinetics, pathophysiology, clinical presentation, and diagnosis and treatment of human BA poisoning.Methods
We searched MEDLINE (1946 to present), EMBASE (1947 to present), SCOPUS, The Indonesia Publication Index (http://id.portalgaruda.org/), ToxNet, book chapters, Google searches, Pro-MED alerts, and references from previously published journal articles. We identified a total of 109 references which were reviewed. Of those, 29 (26 %) had relevant information and were included. Bongkrekic acid is a heat-stable, highly unsaturated tricarboxylic fatty acid with a molecular weight of 486 kDa. Outbreaks have been reported from Indonesia, China, and more recently in Mozambique. Very little is known about the toxicokinetics of BA. Bongkrekic acid produces its toxic effects by inhibiting mitochondrial (ANT). ANT can also alter cellular apoptosis. Signs and symptoms in humans are similar to the clinical findings from other mitochondrial poisons, but they vary in severity and time course. Management of patients is symptomatic and supportive.Conclusions
Bongkrekic acid is a mitochondrial ANT toxin and is reported primarily in outbreaks of food-borne poisoning involving coconut and corn. It should be considered in outbreaks of food-borne illness when signs and symptoms manifest involving the liver, brain, and kidneys and when coconut- or corn-based foods are implicated.5.
6.
Badria A. Al Hatali Said A. Al Mazroui Abdullah S. Alreesi Robert J. Geller Brent W. Morgan Ziad N. Kazzi 《Journal of medical toxicology》2015,11(2):242-244
Background
Carpet vipers (Echis) are found across the semiarid regions of west, north, and east Africa; west, south, and east Arabia; parts of Iran and Afghanistan north to Uzbekistan; and in Pakistan, India, and Sri Lanka. Recently, a new species belonging to the Echis genus, Echis omanensis has been recognized in Oman. Not much is known about the clinical manifestations of envenomation from its bite.Case Report
A 63-year-old snake keeper presented to the emergency department shortly after being bitten by an Oman carpet viper (E. omanensis). The incident occurred during expression of the venom at a research center. The patient complained of severe pain and swelling of the left index finger, which extended to the mid-forearm within 1 h. His vital signs remained stable, with no evidence of systemic manifestations. He was treated initially with analgesics and tetanus toxoid. Due to rapidly progressive swelling and the potential for a delayed coagulopathy, the Saudi National Guard polyvalent snake antivenom was administered according to the Ministry of Health protocol. The patient was admitted to the intensive care unit, remained hemodynamically stable, and had normal serial coagulation tests, with subsequent resolution of the swelling.Conclusion
We report the first case of an E. omanensis bite in which the patient developed rapidly progressive local toxicity, which improved after administration of the Saudi polyvalent antivenom. 相似文献7.
8.
9.
This article highlights perceived weaknesses in the current understanding of unilateral client exit from alcohol and other drug psychosocial treatment. It is argued that unilateral client exit is typically interpreted as a "failure of retention" when it could equally be interpreted as a "failure of treatment fit"; that is, the failure to deliver treatment optimally suited to actual client attendance. The results from an exploratory study conducted within a failure of treatment fit framework are presented. This study explored the possibility that short-term outpatient alcohol and other drug (AOD) treatment attendance may be an intentional service use strategy and that short-term attendees may exit AOD treatment as satisfied, successful, consumers. Standardized questionnaires were administered to clients (n = 109) starting a new treatment episode between June-August 2003 at admission and two-months post admission. Questionnaires explored the accuracy of client estimates of future appointment attendance, the reasons for short-term service exit, the satisfaction and outcome ratings of short-term clients, and the extent to which these compared with their longer-term peers. Findings suggest short-term treatment attendance is not an intentional service use strategy. However, despite attending fewer appointments than intended, most short-term participants reported significant levels of service satisfaction and problem improvement, and at a level comparable with their longer term peers. Problem-improvement was endorsed as the number one reason for short-term service exit. Implications for treatment delivery are discussed in light of these findings. 相似文献
10.
Purpose. The purpose of this study was to investigate the influence of hydration characteristics on the in vitro release of 5-fluorouracil from a swellable matrix prepared using a novel triblock copolymer of poly(-caprolactone) and poly(oxyethylene).
Methods. Matrices were prepared by dry compression of mixtures of the drug and copolymer using low compressional forces. Release studies were performed using a custom made rotating basket dissolution apparatus. The positions of the eroding and swelling fronts within the matrices during hydration were monitored using freeze fracture scanning electron microscopy.
Results. Analysis of the release data revealed a predominantly diffusion controlled mechanism. Observations of the swelling characteristics of the copolymer matrices on immersion in Sørensen's buffer at pH 7.4 revealed gel formation and preferential swelling in the radial direction with visible erosion of the matrix after 4h. During hydration, a gradual increase in gel layer thickness was noted prior to the erosion and eventual dissolution of the matrix.
Conclusions. This study demonstrates a means of differentiating the relative importance of the swelling characteristics in determining the release mechanism and subsequent release rate from swellable matrices. 相似文献
11.
《Current medical research and opinion》2013,29(10):1893-1897
ABSTRACTObjective: A rapidly absorbed tablet formulation of paracetamol containing sodium bicarbonate (PS) has been previously shown to be absorbed at least twice as fast as a standard paracetamol tablet (P) at a 1?g dose. In South America and Asia it is customary for patients to take a 500?mg dose of analgesic. The objective of this pharmacokinetic study was to compare the rate of absorption of PS versus P at a 500?mg dose.Research design and methods: An open, randomized, single dose, cross-over study. Thirty Hispanic healthy volunteers randomly received a 500?mg dose taken orally with 50?mL of water 2?h after a standard breakfast. Blood samples were taken up to 10?h post-dose. Plasma concentrations of paracetamol were determined by HPLC with UV detection.Main outcome measures: AUC0–30 min, Cplasma 30 min and Tmax were analyzed non-parametrically by the Wilcoxon's rank sum test. A linear mixed effects model was used to analyze the logarithmically transformed AUC0–∝ and Cmax. Bioequivalence was accepted if the 90% confidence intervals (CI) for the ratio of the means of the primary pharmacokinetic variable AUC0–∝ lay completely within the range 0.80–1.25.Results: AUC0–30 min and Cplasma 30 min were significantly greater and Tmax was significantly shorter (all p < 0.0001) for PS versus P. The formulations were bioequivalent for AUC0–∝ (90% CI 0.99:1.05) and no statistical difference was seen for Cmax (95% CI 0.91:1.14).Conclusions: Paracetamol was absorbed at least twice as fast from PS compared to P at a 500?mg dose. The extent of absorption was equivalent for both formulations. 相似文献
12.
《Pharmaceutical development and technology》2013,18(3):301-309
Response surface methodology (RSM) was applied to optimize the self‐emulsifying drug delivery system (SEDDS) containing 25% (w/w) Drug A, a model drug with a high lipophilicity and low water solubility. The key objective of this study was to identify an optimal SEDDS formulation that: 1) possesses a minimum concentration of the surfactant and a maximum concentration of lipid and 2) generates a fine emulsion and eliminates large size droplets (≥ 1 µm) upon dilution with an aqueous medium. Three ingredient variables [PEG 400, Cremophor EL, and a mixture of glycerol dioleate (GDO), and glycerol monooleate (GMO)] were included in the experimental design, while keeping the other ingredients at a fixed level (25% Drug A, 6% ethanol, 3% propylene glycol, 4% water, and 2% tromethamine) in the SEDDS formulation. Dispersion performance of these formulations upon dilution with a simulated gastrointestinal fluid was measured, and the population of the large droplets was used as the primary response for statistical modeling. The results of this mixture study revealed significant interactions among the three ingredients, and their individual levels in the formulation collectively dictated the dispersion performance. The fitted response surface model predicted an optimal region of the SEDDS formulation compositions that generate fine emulsions and essentially eliminates large droplets upon dilution. The predicted optimal 25% Drug A–SEDDS formulations with the levels of Cremophor EL ranging from 40–44%, GDO/GMO ranging from 10–13%, and PEG 400 ranging from 2.7–9.0% were selected and prepared. The dispersion experiment results confirmed the prediction of this model and identified potential optimal formulations for further development. This work demonstrates that RSM is an efficient approach for optimization of the SEDDS formulation. 相似文献
13.
Mutation trend of hemagglutinin of influenza A virus: a review from a computational mutation viewpoint 总被引:1,自引:0,他引:1
Since 1999 we have developed two computational mutation approaches to analyze the protein primary structure whose methodology and implications were reviewed in 2002. Our first approach is the calculation of predictable and unpredictable portions of amino-acid pairs in a protein, and the second is the calculation of amino-acid distribution rank in a protein. Both approaches provide quantitative measures to present a protein, which we have used to study a number of proteins with numerous mutations such as p53 proteins. More recently, we focussed our efforts on analyzing the proteins mutating frequently over time such as hemagglutinins of influenza A viruses. In this review we summarise our findings and their implications for hemagglutinin mutations in combination with some newly available data. Our approaches throw light on the true nature of genetic heterogeneity of influenza virus hemagglutinins; that is, the protein variability is highly relevant to its amino-acid construction. Using these approaches, we can monitor new mutations from influenza virus hemagglutinins and may predict their mutations in the future. 相似文献
14.
Kojima T Higashi K Suzuki T Tomono K Moribe K Yamamoto K 《Pharmaceutical research》2012,29(10):2777-2791
Purpose
The stabilization mechanism of a supersaturated solution of mefenamic acid (MFA) from a solid dispersion with EUDRAGIT? EPO (EPO) was investigated.Methods
The solid dispersions were prepared by cryogenic grinding method. Powder X-ray diffractometry, in vitro dissolution test, in vivo oral absorption study, infrared spectroscopy, and solid- and solution-state NMR spectroscopies were used to characterize the solid dispersions.Results
Dissolution tests in acetate buffer (pH 5.5) revealed that solid dispersion showed > 200-fold higher concentration of MFA. Supersaturated solution was stable over 1?month and exhibited improved oral bioavailability of MFA in rats, with a 7.8-fold higher area under the plasma concentration-versus-time curve. Solid-state 1H spin–lattice relaxation time (T1) measurement showed that MFA was almost monomolecularly dispersed in the EPO polymer matrix. Intermolecular interaction between MFA and EPO was indicated by solid-state infrared and 13C-T1 measurements. Solution-state 1H-NMR measurement demonstrated that MFA existed in monomolecular state in supersaturated solution. 1H-T1 and difference nuclear Overhauser effect measurements indicated that cross relaxation occurred between MFA and EPO due to the small distance between them.Conclusions
The formation and high stability of the supersaturated solution were attributable to the specifically formed intermolecular interactions between MFA and EPO. 相似文献15.
16.
Introduction
The aim of the PROMIS® Smoking Initiative is to develop, evaluate, and standardize item banks to assess cigarette smoking behavior and biopsychosocial constructs associated with smoking for both daily and non-daily smokers.Methods
We used qualitative methods to develop the item pool (following the PROMIS® approach: e.g., literature search, “binning and winnowing” of items, and focus groups and cognitive interviews to finalize wording and format), and quantitative methods (e.g., factor analysis) to develop the item banks.Results
We considered a total of 1622 extant items, and 44 new items for inclusion in the smoking item banks. A final set of 277 items representing 11 conceptual domains was selected for field testing in a national sample of smokers. Using data from 3021 daily smokers in the field test, an iterative series of exploratory factor analyses and project team discussions resulted in six item banks: Positive Consequences of Smoking (40 items), Smoking Dependence/Craving (55 items), Health Consequences of Smoking (26 items), Psychosocial Consequences of Smoking (37 items), Coping Aspects of Smoking (30 items), and Social Factors of Smoking (23 items).Conclusions
Inclusion of a smoking domain in the PROMIS® framework will standardize measurement of key smoking constructs using state-of-the-art psychometric methods, and make them widely accessible to health care providers, smoking researchers and the large community of researchers using PROMIS® who might not otherwise include an assessment of smoking in their design. Next steps include reducing the number of items in each domain, conducting confirmatory analyses, and duplicating the process for non-daily smokers. 相似文献17.
18.
Srinivas Nalamachu Ernest A. Kopecky Robert Taylor Jr Ben Vaughn Melinda O’Connor 《Current medical research and opinion》2016,32(7):1311-1317
Background: Abuse deterrent formulations (ADF) are designed to prevent the misuse of opioids by tampering (e.g. physical and chemical manipulation) in order to ingest the opioid in a manner other than intended. Extended-release (ER) formulations are formulated with a larger drug load than immediate-release (IR) formulations, which makes ER opioids more desirable to drug abusers than I.R. formulations. ADFs, therefore, are particularly useful with ER opioid agents, which are designed to produce consistent analgesia over prolonged dosing intervals. However, the drug release properties of these formulations vary and sometimes may not provide adequate pain relief throughout the intended dosing interval, requiring patients to take additional medication for pain relief. Oxycodone DETERx* (Xtampza ER*) is a novel, microsphere-in-capsule opioid formulation, which allows for twice daily dosing (i.e. every 12?hours) and mitigates the ability to tamper with the formulation.Objective: To evaluate the durability of pain relief of a novel formulation of oxycodone throughout the 12?hour dosing interval.Research design and methods: This study is a post-hoc analysis of 193 subjects in a Phase 3 randomized withdrawal, double-blind, placebo-controlled, enriched-enrollment, parallel-group, multicenter, 12-week clinical study.Main outcome measures: The analysis evaluated the frequency and distribution of use of oxycodone ER and rescue medication during the Double-blind Maintenance Phase of the study.Results: Usage patterns captured by an electronic diary indicated limited overall and limited per-day use of rescue medication with no increase in rescue medication consumption 8 to 12?hours post-dose, suggesting that subjects did not experience end-of-dose failure during this time period.Limitations: This study is limited in that it is a post-hoc analysis based on data gathered electronically from a large, prospective, double-blind, randomized, placebo-controlled, Phase 3 clinical study.Conclusion: The evaluation of dosing patterns indicates that this ER oxycodone capsule formulation has durability of effect over the entire 12-hour dosing interval. These data support the use of abuse-deterrent oxycodone ER as a 12-hour dosing formulation. 相似文献
19.
《Toxicology mechanisms and methods》2013,23(9):515-525
The safety of Garcinia cambogiaextract, its active ingredient (–)-hydroxycitric acid (HCA), and the marketed weight management formula, Super CitriMax® (HCA-SX), is supported by numerous in vitro and animal experimental studies as well as several clinical studies. HCA-SX has been shown to reduce appetite, inhibit fat synthesis, and decrease body weight. A series of toxicological tests including acute, short-term, and sub-chronic studies as well as teratogenicity/reproduction and genotoxicity studies were performed on HCA-SX. In the acute oral toxicity study, administration of a single dose of 5,000?mg/kg of HCA-SX did not reveal any significant changes for all examined tissues. Following the high dose safety testing, there were no remarkable changes or differences observed in any of the experimental conditions monitored. There were no macroscopic abnormalities for any examined tissues at scheduled necropsies. On the basis of these findings, the consumption of HCA-SX at dose level of up to 4667?mg/day is considered safe. 相似文献