Elucidation of in vitro phase I metabolites of droperidol using UPLC-QTOF MS.

Droperidol, an antidopaminergic drug clinically used as an antiemetic and antipsychotic, has been reported to induce cardiac toxicity in patients. Due to the close relationship between drug metabolism and efficiency and toxicity, the present study aims to investigate the phase I metabolites using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The NADPH-supplemented phase I incubation system was used to elucidate the in vitro phase I metabolites. Five metabolites were detected after droperidol was incubated with phase I incubation mixture, including one hydrogenated droperidol, three oxidative metabolites, and one N-dealkylated droperidol, elucidated by individual retention time and MS/MS fragmentation. Due to the existed phase II metabolic reaction, further phase II metabolism should be investigated in the future. In conclusion, the phase I metabolism of droperidol was investigated in the present study, and five new metabolites were identified. The efficiency and toxicity of these phase I metabolites should be investigated in the future.

Compatibility of butorphanol and droperidol in 0.9% sodium chloride injection.

PURPOSE: The compatibility and stability of butorphanol tartrate and droperidol in polyvinyl chloride (PVC) bags and glass bottles stored at 4°C and 25°C for up to 15 days were studied. METHODS: Admixtures were assessed initially and for 15 days after preparation in PVC bags and glass bottles using 0.9% sodium chloride injection as a diluent and stored at 4°C and 25°C. The initial drug concentrations were 0.08 mg/mL for butorphanol tartrate and 0.05 mg/mL for droperidol. Samples were withdrawn from each container immediately after preparation and at predetermined intervals (2, 4, 8, 24, 48, 72, 120, 168, 240, and 360 hours after preparation). The solutions were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. Drug concentrations were determined using a validated high-pressure liquid chromatography method. RESULTS: After 15 days of storage, all formulations tested retained >98% of the initial concentrations of both drugs. The drug mixtures were clear in appearance, and no color change or precipitation was observed. Throughout this period, pH values remained stable. CONCLUSION: Admixtures of butorphanol tartrate 0.08 mg/mL and droperidol 0.05 mg/mL in 0.9% sodium chloride injection were stable for at least 360 hours when stored in PVC bags or glass bottles at 4°C and 25°C and protected from light.

The pharmacokinetics of droperidol in anesthetized patients.

A pharmacokinetic study of droperidol was performed in ten anesthetized patients receiving an intravenous bolus dose of 150 micrograms/kg of droperidol. Plasma concentrations were measured using a specific radioimmunoassay method. The pharmacokinetics of droperidol can be described according to a three-compartment open model. The mean (+/- SD) half-life for the rapid (t 1/2 pi) and slow distribution t 1/2 alpha) phases was 1.4 +/- 0.5 min and 14.3 +/- 6.5 min, respectively. The mean elimination half-life, t 1/2 beta was 103.8 +/- 20.2 min. The mean (+/- SD) total body clearance was 14.1 +/- 4.4 ml X min-1 X kg-1, and the total apparent volume of distribution (Vd beta) was 2.04 +/- 0.50 l/kg. The short terminal half-life of droperidol does not correlate with the well-known, relatively prolonged duration of its pharmacologic action.

[Pharmacodynamics of the interaction of neuroleptanalgetics]. / Izuchenie farmakodinamiki vzaimodeistviia neiroleptanal'getikov.

The authors carried out a quantitative assessment of pharmacodynamic effects of droperidol (5 and 25 mg/kg) and phentanyl (0.5 and 1 microgram/kg). The effects of the drugs on sensitivity and pain were studied by the "tail jerking" test. The electrophysiological studies included spectral analysis of the EG of the following central nervous system structures: head of the caudate nucleus, substantia nigra, central gray of the midbrain. The quantitative characteristics of the analgesic effect of phentanyl and hyperalgetic effect of droperidol, as well as the potentiation of the antinociceptive effect of phentanyl combined with droperidol were demonstrated. Studies on the EG recorded the appearance of local extremes on the spectrograms within the range of 7 Hz. The use of the method of least squares for comparing the curves of the relationships between the effects of droperidol and phentanyl and their concentrations in the brain enabled deriving the equations that quantitatively characterize the pharmacodynamic effects of interaction of the drugs in question.

[Anesthesiological management of the high-risk surgical patient]. / Trattamento anestesiologico del paziente chirurgico ad alto rischio.

Evaluation of the anaesthesiological risk in surgical patients is described and an account is given of results obtained with an association of ketamin and NLA II in 57 high-risk patients subjected to general surgical management.

De la neuroleptoanalgesia a la anestesia analgésica

Detalle de la evolución de las técnicas anestésicas, de los componentes fundamentales de la anestesia:analgesia, protección neurovegetativas, hiporosis y relajación muscular. Química y farmacología y efectos adversos de los analgésicos centrales, morfinominéticos, neurolépticos. Asociaciones empleadas y farmacología de los medicamentos utilizados. Métodos de la neuroleptoanalgesia tipo I y II de la anestesia analgésica

De la neuroleptoanalgesia a la anestesia analgésica

Detalle de la evolución de las técnicas anestésicas, de los componentes fundamentales de la anestesia:analgesia, protección neurovegetativas, hiporosis y relajación muscular. Química y farmacología y efectos adversos de los analgésicos centrales, morfinominéticos, neurolépticos. Asociaciones empleadas y farmacología de los medicamentos utilizados. Métodos de la neuroleptoanalgesia tipo I y II de la anestesia analgésica