Determination of the anxiolytic agent 8-chloro-6-(2-chlorophenyl)-4H-imidazo-[1,5-alpha] [1,4]-benzodiazepine-3-carboxamide in whole blood, plasma or urine by high-performance liquid chromatography.
A rapid, sensitive and specific high-performance liquid chromatographic (HPLC) assay was developed for the determination of 8-chloro-6-(2-chlorophenyl)-4H-imidazo-[1,5-alpha]-[1,4]-benzodiazepine-3-carboxamide [I] and its 4-hydroxy metabolite, 8-chloro-6-(2-chlorophenyl)-4-hydroxy-4H-imidazo-[1,5-alpha] [1,4]-benzodiazepine-3-carboxamide [II] in whole blood, plasma or urine. The assay for both compounds involves extraction into diethyl ether-methylene chloride (70:30) from blood, plasma, or urine buffered to pH 9.0. The overall recoveries of [I] and [II] are 92.0 +/- 5.4% (S.D.) and 90.3 +/- 4.9% (S.D.), respectively. The sensitivity limit of detection is 50 ng/ml of blood, plasma, or urine using a UV detector at 254 nm. The HPLC assay was used to monitor the blood concentration-time fall-off profiles, and urinary excretion profiles in the dog following single 1 mg/kg intravenous and 5 mg/kg oral doses, and following multiple oral doses of 100 mg/kg/day of compound [I].
Midazolam compared with thiopentone as a hypnotic component in balanced anaesthesia: A randomized, double-blind study
SummaryMidazolam is a short-acting water soluble benzodiazepine derivative. It is a hypnotic used for intravenous anaesthesia induction. The present investigation was designed in a prospective double-blind fashion to compare midazolam with thiopentone as hypnotic components in balanced anaesthesia. The study included 50 healthy patients undergoing relatively short surgical procedures. The results revealed that thiopentone is faster in onset than midazolam for induction of anaesthesia, with less variation of dose response. However, maintenance of anaesthesia was superior with midazolam, requiring fewer supplemental anaesthetic drugs, having better patient acceptance and providing more amnesia. Postoperative complications were very low with both techniques. Midazolam was surprisingly similar to thiopentone in most parameters including emergence time from anaesthesia. Midazolam is a new drug with potential both for induction of anaesthesia and maintenance of balanced anaesthesia.RésuméLe midazolam est un dirivé hydrosoluble de la benzodiazépine à action courte qui peut être employé par la voie veineuse pour l’induction de l’anesthésie. On compare dans la présente étude les effets hypnotiques du midazolam avec ceux du thiopental lors de l’anesthésie générale balancée en utilisant une méthode prospective à double insu. L’étude englobe cinquante patients en bon état subissant des interventions d’une durée relativement courte. Les résultats montrent qu’à l’induction, l’action du thiopental débute plus rapidement que celle du midazolam et que la relation dose-effet est moins variable.Cependant, pour le maintien de l’anesthésie, le midazolam a été considéré supérieur. Moins d’agents anesthésiques supplémentaires ont été requis, l’acceptance par le patient a été plus grande et l’amnésie supérieure. Avec les deux techniques, les complications ont été très minimes. La comparaison de la plupart des paramètres incluant la durée de la période de réveil démontre la suprenante similarité des deux agents. En conclusion, le midazolam est un nouvel agent qui pourrait s’avérer très utile pour l’induction et ce maintien de l’anesthésie générale balancée.
INTRAVENOUS ANAESTHESIA WITH DIAZEPAM
b. Relaxation of striated muscles induced by a central action. In clinical practice, the sedative action has proved valuable in a variety of conditions, such as sleep disturbances3, as premedication for surgery4, together with topical anaesthesia for bronchoscopy* and as single anaesthetic agent for cardioversion6. The muscle-relaxing effect is taken advantage of in various spastic disorders5 as well as in tetanus2. In animal experiments, diazepam has a very high safety index without depression of respiration and only slight lowering of blood pressure with high doses’. In patients undergoing diagnostic cardiac catherization, Nutter and Massumi (1 965)6 monitored EGG, direct arterial blood pressure, pneumograms and blood gases during intravenous administration of diazepam. They observed no depression of the cardiorespiratory function from the drug. Prompted by these results we started to inject diazepam intravenously during anaesthesia, originally to see if it produced sufficient muscular relaxation for the performance of laparotomy and tracheal intubation. We were, however, much more impressed by the sedative, sleep-inducing action of this drug and came to use it as an induction agent instead of thiopentoneg. After inducing sleep in more than 300 patients with diazepam, we are here presenting our experiences with the drug as an induction agent, comparing it with thiopentone. We have tried to determine the dose necessary to produce sleep, the duration of the sleep as well as the degree of amnesia. Furthermore, an attempt have been made to determine the dose of muscle relaxants needed