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Paul Rolan Stephen Lim Vivian Sunderland Yandi Liu Valeria Molnar 《British journal of clinical pharmacology》2014,77(6):1011-1016
Aim
The principal study objective was to investigate the pharmacokinetic characteristics of a new sublingual ketamine wafer and to establish its absolute bioavailability and local tolerability.Methods
The study was of open label, two way randomized crossover design in eight healthy male volunteers. Each participant received either a single 10 mg intravenous dose as a constant rate 30 min infusion or a 25 mg sublingual dose of ketamine wafer in two treatment periods with a 7 day wash out. Pharmacokinetic blood sampling and local tolerability and safety assessments were carried out during 24 h following both dosing occasions. Plasma concentrations were analyzed by non-compartmental methods and local tolerability was assessed using modified Likert scales.Results
The median (90% CI lower, upper limit) absolute bioavailability of sublingual ketamine was 29% (27, 31%). The first quantifiable plasma ketamine concentration was observed within 5 min for all eight participants for both routes of administration and the median (min–max) time of the peak plasma concentration was 0.75 h (0.25–1.0 h) after sublingual administration. The ketamine wafer had very good local tolerability.Conclusion
Sublingual administration of the ketamine wafer resulted in rapid absorption. The ketamine wafer has comparable bioavailability with other oral transmucosal formulations of ketamine but with markedly reduced inter-subject variability, warranting further evaluation as an analgesic adjunct. 相似文献48.
Neil Dawson Martin McDonald Desmond J Higham Brian J Morris Judith A Pratt 《Neuropsychopharmacology》2014,39(7):1786-1798
Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia. 相似文献
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目的综述各种生物检材中提取检测氯胺酮及其代谢物的方法。方法参考国内外相关文献,介绍了各生物检材特点,并列举了多种预处理和分析方法的优势与不足。结果由于氯胺酮的特殊药理作用,其娱乐性滥用现象较为严重和普遍,因此被列入新型毒品范畴。本文综述了几种快速、准确地检测出人体内氯胺酮及其代谢物的方法,并对各方法特点进行了总结概括。结论氯胺酮生物检材的提取检测方法正沿着更加方便、快速、准确的方向发展。 相似文献
50.
Bioerodable Ketamine-Loaded Microparticles Fabricated Using Dissolvable Hydrogel Template Technology
Minze Zhu Andrew K. Whittaker Maree T. Smith Felicity Y. Han 《Journal of pharmaceutical sciences》2019,108(3):1220-1226
For severe cancer-related pain that is not relieved adequately by escalating doses of oral or parenterally administered strong opioid analgesics such as morphine, alone or in combination with an adjuvant drug such as ketamine, more invasive dosing routes may be warranted. One such approach involves surgical implantation of an intrathecal pump to deliver small doses of analgesic or adjuvant drugs in close proximity to the receptors that transduce their pain-relieving effects. However, the use of implanted devices is associated with a range of catheter-related problems. To address this, we have developed biodegradable microparticles loaded with the analgesic adjuvant drug, ketamine, for sustained release after a single bolus intrathecal injection. Drug-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared using a dissolvable hydrogel template. Using PLGA with 3 different ratios of lactic acid to glycolic acid (L/G), relatively high ketamine loading and homogenous particle shape and size were achieved. Specifically, ketamine loading of PLGA5050, PLGA7525, and PLGA8515 in ester-terminated microparticles was 20.0%, 20.4%, and 18.9%, respectively. The microparticles were within the desired size range (20 μm diameter and 30 μm height) and in vitro release was sustained for ≥14 days with an acceptable initial burst release (~10%-20%) achieved. 相似文献