Thiopental elimination

The test is conducted by using the mechanically congested A. centralis of the rabbit ear. The injection is directed into the distal direction. A 7,5 % solution of thiopental can serve as a positive control because it induces severe inflammatory reactions. The further procedure includes evaluation scores being used as for the i.v. injections. To eliminate the species-specific influence of small rodents (small artery) it is also recommended to use non-rodents like the dog. 

Figure 2.13. Kinetics of thiopental distribution. Thiopental is a very hydrophobic barbiturate that is used for transient narcosis. Duration of the narcosis is limited by redistribution of thiopental from the brain to other body compartments (which is very fast) rather than elimination of the drag (which is very slow).

All three barbiturates are primarily eliminated by hepatic metabolism and renal excretion of inactive metabolites a small fraction of thiopental undergoes desulfuration to the longer-acting hypnotic pentobarbital. Each drug is highly protein bound (Table 13-2). Hepatic disease or other conditions that reduce serum protein concentration will decrease the volume of distribution and thereby increase the initial free concentration and hypnotic effect of an induction dose. 

The high lipophilicity of thiopental ensures rapid entry to the CNS following an intravenous bolus dose. As the blood level falls, thiopental exits the brain and is redistributed to other highly perfused tissues such as the liver and skeletal muscles. Thus, the brain level of thiopental rapidly declines to the point that consciousness is regained within a few minutes. Ultimately, the elimination of thiopental depends on its metabolism by the liver, but only 10-15% of thiopental is metabolized per hour. The answer is (D). 

Diethyl malonate on reaction with sodium metal gives rise to sodium malonic ester which on treatment with ethyl bromide results into the formation of diethyl ester of ethyl malonic acid with the elimination of hydrobromic acid. The resulting ester on further reaction with 2-bromopentane gives the desired eompound, i.e., diethyl ester of ethyl (1-methyl butyl) malonic acid which on subsequent treatment with thiourea forms thiopental with the elimination of two moles of ethanol. Ultimately, the enol-iorm of thiopental when reaeted with a ealeulated amoimt of sodium hydroxide, it gives thiopental sodium. 

In man, hydrolysis of the thiobarbiturate ring of thiopeiital does not occur [58], and biotransformation by the liver microsomal oxidase system appears to be the main route of elimination from the body [59]. However, in spite of the many studies of thiobarbiturate metabolism, the fate of the majority of the administered dose is yet to be identified [58]. What is clear is that less than 0.5% of the dose is excreted as unchanged thiopental [35,60]. 

Pharmacokinetic constants for the absorption and elimination of pralid-oxime have been determined in man83. a pharmacokinetic model for flow, lipid solubility, protein binding and saturation-IImited metabolism of thiopental has permitted the a priori prediction of bodily distribution conslsten with experiment . Imipramine and its metabolites are rapidly distributed in the rat and renally and biliary excreted with enterohepatic circulation . Mathematical models have been established for the pharmacokinetics of neurohypophysial and related peptides . The oral administration of 2,3,5, triiodebenzoic acid in goats and a cow by whole-body radioactivity retention showed a rapid distributive and subsequent exponential elimination phase with the metabolites formed by deiodination . Bishydroxycoumarin shows dose-dependent first order elimination in man but not in other species and has been assigned to dose effects on el imi nation . ... 

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