Inhibition of the active principle of the weak opioid tilidine by the triazole antifungal voriconazole. (1/6)

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Contribution of CYP2C19 and CYP3A4 to the formation of the active nortilidine from the prodrug tilidine. (2/6)

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Gas-chromatographic determination of nanogram amounts of enantiomers of nortilidine, a main metabolite of tilidine, in biological specimens. (3/6)

We report a specific and sensitive method for determination of the individual optical isomers of nortilidine, a main metabolite of tilidine, with the aid of a nitrogen-sensitive detector. With N-trifluoroacetyl-L-leucyl chloride as chiral reagent, the diastereomeric derivatives of the nortilidine enantiomers could be separated and quantified in the nanogram range. Under these conditions, the enantiomers of bisnortilidine, another main metabolite of tilidine, were also separated. Investigations in rats with the enantiomers of tilidine and nortilidine indicated that no racemization occurs during N-demethylation in the organism. After oral and intravenous administration of 50 mg of tilidine.HCI to a human volunteer, identical concentrations of nortilidine enantiomers were found in the plasma.  (+info)

Involvement of the median raphe nucleus in antinociception induced by morphine, buprenorphine and tilidine in the rat. (4/6)

1 Antinociception induced by three analgesics with differing profiles of activity, morphine, buprenorphine and tilidine, have been evaluated in the hot plate and paw pressure tests after administration by the subcutaneous route and directly into the median raphe nucleus in the conscious rat. 2 Behavioural and neurological effects of the three analgesics were also assessed. 3 The typical profiles of antinociceptive activity induced by the three analgesics were qualitatively similar after either route of administration. Morphine induced naloxone-sensitive dose-dependent effects in both tests. Buprenorphine showed naloxone-sensitive effects with a bell-shaped dose-response curve in the thermal test but dose-dependent activity in the pressure test. Tilidine induced naloxone-sensitive dose-dependent effects in the thermal test but demonstrated naloxone-insensitive activity in the paw pressure test. 4 The behavioural and neurological effects of the analgesics in the dose range used would not have affected the animals' ability to respond to the nociceptive stimuli. 5 The results suggest that the median raphe could participate in drug-induced antinociception. The mechanisms by which this might occur are discussed.  (+info)

A new formalism for temporal modeling in medical decision-support systems. (5/6)

We present a new mathematical formalism, which we call modifiable temporal belief networks (MTBNs) that extends the concept of an ordinary belief network (BN) to incorporate a dynamic causal structure and explicit temporal semantics. An important feature of MTBNs is that they allow portions of the model to be abstract and portions of it to be temporally explicit. We show how this property can lead to substantial knowledge acquisition and computational complexity savings. In addition to temporal modeling, the language of MTBNs can be an important analytical tool, as well as temporal language for causal discovery.  (+info)

HPLC determination of ketamine, norketamine, and dehydronorketamine in plasma with a high-purity reversed-phase sorbent. (6/6)

We developed an isocratic, selective, and very sensitive HPLC method for the determination of ketamine and its two main metabolites in plasma. The compounds were extracted from plasma by a liquid-liquid extraction with a dichloromethane:ethyl acetate mixture followed by an acidic back-extraction. Separation was achieved on a new stationary phase, Purospher RP-18 endcapped, with a mobile phase containing acetonitrile:0.03 mol/L phosphate buffer (23:77 by vol) adjusted to pH 7.2. Because of the high column efficiency and the significant improvement of peak symmetry, the quantification limit could be down to 5 micrograms/L for ketamine and norketamine (NK). The intraday and interday CVs ranged from 1.7% to 5.8% and 3.1% to 10.2% for all compounds respectively. The method is sensitive enough for monitoring ketamine, NK, and dehydroketamine in plasma during pharmacokinetic studies after an intravenous bolus of a low dose of ketamine.  (+info)