Pentobarbital absorption

Ueda S, Yamaoka K and Nakagawa T (1999) Effect of Pentobarbital Anaesthesia on Intestinal Absorption and Hepatic First-Pass Metabolism of Oxacillin in Rats, Evaluated by Portal-Systemic Concentration Difference. J Pharm Pharmacol 51 pp 585-589. 

What is the difference between the drugs thiopental and pentobarbital and how would it affect their absorption and distribution ... 

CRITICAL ASSESSEMENT OF THE METHOD In general pharmacological studies during anesthesia should be assessed appropriately due to the possible interaction between the test compound and the used anesthetic as well as due to the reduced tone of the autonomic nervous system. Enteral administration of the candidate compound should be avoided, because enteral absorption of the test compound might be reduced due to the impaired intestinal motility during anesthesia. With respect to the effect of the aesthetic compound itself on intermediary metabolism the barbiturate pentobarbital sodium is the most inert anesthetic and does not cause alterations of metabolic blood and tissue parameters. In contrast, e.g. urethane as well as isoflurane (inhalation aesthetic) influences by itself substantially metabolic parameters over time (hours). 

For ex vivo assays, mice, rats, or guinea pigs from either sex receive the test compound or the vehicle (for controls) by oral, intraperitoneal or intravenous administration. At the end of the absorption time, blood is collected by caval venipuncture under pentobarbital sodium anesthesia and xylazine (8 rng/kg i.m.) premedication. 

Male Sprague-Dawley rats weighing 260-300 g are used. The animals receive the test compound or the vehicle (controls) by oral, intraperitoneal or intravenous administration. After the end of the absorption time (i.p. 30 min, p.o. 60 min, i.v. variable), rats are anesthetized with pentobarbital sodium (i.p.). One carotid artery is cannulated for blood withdrawal and one jugular vein is cannulated for inducer injection. The animals receive an intravenous injection of heparin and 20 min later, approx. 100 il blood are collected (initial value). Ten min later, the thrombocytopenia-inducing substance collagenase is administered intravenously. 

The two polymorphs of the barbiturate pentobarbital exhibit significantly different rates of absorption and area under the curve for oral administration (Fig. 7.1) (Draguet-Brughmans et al. 1979). Comparison of rectal absorption of suppositories containing the two polymorphs of indomethacin showed higher levels for the a... 

Fig. 7.1 Rate of absorption of the two polymorphs of orally administered pentobarbital, a, Form I b, Form II. (From Draguet-Brughmans et al. 1979, with permission.)...

Compare the rate of absorption of pentobarbital through its routes of administration. 

Thiopental has UV absorption maxima at 290 nm and 305 nm in acidic and alkaline media, respectively. In contrast, the oxobarbitnrates have absorption maxima at 220 nm and 255 tun, respectively [46]. These differences provided a means of distinguishing thiopental from its major metabolite, pentobarbital, and as a consequence most determinations were carried out at around 280 nm [33,35,45]. In one case greater selectivity was provided by a change in extraction solvent, which permitted the determination of the carboxylic acid metabolite of thiopental [35]. Additional sensitivity could be provided by the use of back-extraction methods (vide supra). 

The pretreatment of rats with desipramine resulted in delayed stomach emptying and, hence, slowed absorption of phenylbutazone, oxyphenbutazone, hydrocortisone, and salicylate.On the other hand, desipramine had no apparent effect on the absorption of orally administered amphetamine or phenobarbital. In another study, the interactions of a variety of acutely and chronically administered contraceptive agents and their effect on pentobarbital narcosis in the rat, as well as on certain metabolic transformations in vitro, were examined. Medroxyprogesterone, alone or in combination with ethynylestradiol, stimulated the metabolism of 7nitroanisole, aminopyrine, and aniline in vitro, although these effects cure not as marked as those seen with well-known Inducers such as phenobarbital and pesticides. 

Overturn time in the goldfish is a pharmacologic end point for biologic membrane permeation and has been used in kinetic studies with pentobarbital and ethanol s The absorption of 3-Methoxy-N-methyI-morphinan, pKa 8.0, from the rat stomach at pH 2.0, has been assigned to the formation of ion pairs of significant lipid solubility The... 

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