Pharmacokinetics and Anesthetic Potency of a Thiopental Isomer

• Published in: Journal of pharmaceutical sciences 1983-08, Vol.72 (8), p.937-940
• Main Authors: Stanskix, Donald R., Burch, Patrick G., Harapat, Sandra, Richards, Richard K.
• Format: Article
• Language: English
• Subjects: Anesthetic agents-potency of a thiopental isomer in mice; Anesthetic agents—potency of a thiopental isomer in mice, comparison with thiopental; anesthetic potency in mice; Anesthetics; Animals; Chromatography, High Pressure Liquid - methods; comparison with thiopental; Female; Humans; Isomerism; Kinetics; Lethal Dose 50; Male; Mice; pharmacokinetics in humans; Pharmacokinetics-of a thiopental isomer in humans; Pharmacokinetics—of a thiopental isomer in humans, comparison with thiopental; Thiopental - analogs & derivatives; Thiopental - metabolism; Thiopental - pharmacology; Thiopental - toxicity; Thiopental-isomer determination in serum by high-performance liquid chromatography; Thiopental—isomer determination in serum by highperformance liquid chromatography, pharmacokinetics in humans, anesthetic potency in mice; Thiopental—isomer determination in serum by high‐performance liquid chromatography, pharmacokinetics in humans, anesthetic potency in mice
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600720824

□ In developing a high-performance liquid chromatographic assay for thiopental [5-ethyl-5-(l-methylbutyl)-2-thiobarbituric acid], a thiopental isomer [5-ethyl-5-(l-ethylpropyl)-2-thiobarbituric acid] was found. This isomer occurs (6–7%) in supposedly pure thiopental and in the commercially available thiopental sodium administered to patients for induction of anesthesia. A similar type of isomer also occurs in pentobarbital, the oxybarbiturate analogue of thiopental. Because the disposition and anesthetic potency of the isomer is unknown, its pharmacokinetic properties were determined in humans and its anesthetic potency in mice. In five surgical patients, the terminal elimination halflife, clearance, and volume of distribution at steady state of the isomer were not statistically different from those of thiopental. In mice, the isomer proved to be as effective as thiopental for induction of anesthesia. The LD50 and sleep time at one-half the LD50 did not statistically differ between the two compounds in mice. The close structural similarity of thiopental and the isomer results in similar pharmacokinetic and anesthetic properties. It does not appear critical that the isomer be separated from thiopental in subsequent pharmacological research.