Pharmacokinetics ethanol

After oral ingestion, ethanol pharmacokinetics must take into account (1) Absorption from the gastrointestinal tract. Since ethanol is absorbed most efficiently from the small intestines, the rate of gastric emptying is an important factor that governs the rate of rise of blood alcohol concentration (BAC), i.e., the slope of the ascending limb of the BAC-time curve, and the extent of first pass metabolism of ethanol by the liver and stomach. (2) Distribution of ethanol in the body. Ethanol distributes equally in total body water, which is related to the lean body mass of the person, and (3) the elimination of ethanol from the body, which occurs primarily by metabolism in the liver, first to acetaldehyde and then to acetate [7]. 

Levitt, D.G., PKQuest measurement of intestinal absorption and first pass metabolism — Application to human ethanol pharmacokinetics, BMC Clin. Pharmacol, 2, 4, 2002. 

Norberg A, Jones AW, Hahn RG, Gabrielsson JL. Role of variability in explaining ethanol pharmacokinetics Research and forensic applications. Clin Pharmacokinet 2003 42 1-31. 

Savage IT, James IM. The effect of Hydergine on ethanol pharmacokinetics in mm.JPharm Pharmacol (1993) 45 (Suppl 2), 1119. 

Dorian P, Sellers EM, Reed KL, Warsh JJ, Hamilton C, Kaplan HL, Fan T. Amitriptyline and ethanol pharmacokinetic and pharmacodynamic interaction. EurJ Clin Pharmacol (1983)... 

Alcohol dehydrogenase is a cytoplasmic enzyme mainly found in the liver, but also in the stomach. The enzyme accomplishes the first step of ethanol metabolism, oxidation to acetaldehyde, which is further metabolized by aldehyde dehydrogenase. Quantitatively, the oxidation of ethanol is more or less independent of the blood concentration and constant with time, i.e. it follows zero-order kinetics (pharmacokinetics). On average, a 70-kg person oxidizes about 10 ml of ethanol per hour. 

Alcohol can affect the metabolism of trichloroethylene. This is noted in both toxicity and pharmacokinetic studies. In toxicity studies, simultaneous exposure to ethanol and trichloroethylene increased the concentration of trichloroethylene in the blood and breath of male volunteers (Stewart et al. 1974c). These people also showed "degreaser s flush"—a transient vasodilation of superficial skin vessels. In rats, depressant effects in the central nervous system are exacerbated by coadministration of ethanol and trichloroethylene (Utesch et al. 1981). 

Kaneko T, Wang P-Y, Sato A. 1994. Enzymes induced by ethanol differently affect the pharmacokinetics of trichloroethylene and 1,1,1-trichloroethane. Occup Environ Med 51 113-119. 

The effects of ethanol on bodily functions, e.g., those of the brain, heart, and liver, are dependent upon the systemic concentrations of ethanol over time. Therefore, the pharmacokinetics of ethanol play a pivotal role in the pharmacodynamic actions of ethanol and of its metabolic product acetaldehyde [6],... 

Robinson DL, Brunner LJ, Gonzales RA. 2002. Effect of gender and estrous cycle on the pharmacokinetics of ethanol in the rat brain. Alcohol Clin Exp Res 26(2) 165-172. 

Oxycodone/Lorazepam/Ethanol Multiple oral doses of pregabalin were coadministered with oxycodone, lorazepam, or ethanol. Although no pharmacokinetic interactions were seen, additive effects on cognitive and gross motor functioning were seen when pregabalin was coadministered with those drugs. 

Pharmacokinetics. Seed oil, administered intramuscularly to dogs at a dose of 1 mL/kg labeled glyceryl trioleate injected with the oil, was distributed primarily to iliac nodes, heart, liver, and lungs 5 Phytotoxic effect. Ethanol (95%) extract of the dried seed oil, at a concentration of 500 ppm, was inactive. The biological activity reported has been patented " k Prostaglandin induction. Seed oil, administered subcutaneously to rats at a dose of 1 g/day for 14 days, stimulated PGl-2 synthesis in the thoracic aorta . ... 

Animal studies Early pharmacokinetic studies in mice report that maximum plasma concentrations of hypericin and pseudohypericin were reached at six hours and were maintained for at least eight hours. The aqueous-ethanolic SJW extract used in this study contained 1.0 mg of hypericin (77). 

Animal studies Pharmacokinetics of hyperforin after administration of an ethanolic SJW extract (WS 5572, Dr. Willmar Schwabe, Karlsruhe, Germany) to rats were investigated by Biber et al. (72). Maximum plasma levels of approximately 370ng/mL (approximately 690 nM) were reached after three hours. Estimated half-life and clearance values were six hours and 70mL/min/kg, respectively. 

Non-linear pharmacokinetics are much less common than linear kinetics. They occur when drug concentrations are sufficiently high to saturate the ability of the liver enzymes to metabolise the drug. This occurs with ethanol, therapeutic concentrations of phenytoin and salicylates, or when high doses of barbiturates are used for cerebral protection. The kinetics of conventional doses of thiopentone are linear. With non-linear pharmacokinetics, the amount of drug eliminated per unit time is constant rather than a constant fraction of the amount in the body, as is the case for the linear situation. Non-linear kinetics are also referred to as zero order or saturation kinetics. The rate of drug decline is governed by the Michaelis-Menton equation ... 

Interactions between ethanol and other drugs can have important clinical effects resulting from alterations in the pharmacokinetics or pharmacodynamics of the second drug. 

The concept of clearance is useful in pharmacokinetics because clearance is usually constant over a wide range of concentrations, provided that ehmination processes are not saturated. Saturation of biotransformation and excretory processes may occur in overdose and toxic okinetic effects should be considered. If a constant fraction of drug is eliminated per unit time, the elimination follows first-order kinetics. However, if a constant amount of drug is eliminated per unit time, the elimination is described by zero-order kinetics. Some drugs, for example, ethanol, exhibit zero-order kinetics at normal or non-intoxicating concentrations. However, for any drug that exhibits first-order kinetics at therapeutic or nontoxic concentrations, once the mechanisms for elimination become saturated, the kinetics become zero order and clearance becomes variable.3... 

Hamstra DA, Moffat BA, Hall DE, et al. Intratumoral injection of BCNU in ethanol (DTI-015) results in enhanced delivery to tumor—a pharmacokinetic study. JNeurooncol. 2005 73 225-238. 

Fisher, J.W., D. Mahle, and R. Abbas. 1998. A human physiologically based pharmacokinetic model for trichloroethylene and its metabolites, trichloroacetic acid and free trichloro-ethanol. Toxicol Appl Pharmacol. 152(2) 339-359. 

Most peptides and proteins are water-soluble, and therefore D-PBS or saline can be used as a vehicle. Often, however, limited information is available about the solubility properties of novel small molecules, and the choice of a non-toxic vehicle is more difficult. For example, 200 pi of a 5% ethanol solution is equivalent to one beer in humans and may affect behavior. A solution of 20% cyclodextrin has no known side effects in vivo, but in rare cases, some compounds are trapped in the solution and therefore mice have no exposure to the compound. Some vehicles used for in vitro studies can be toxic in live mice. Some vehicles such as methylcellulose have no side effect when given p.o., but are toxic if administered i.v. Access to information about the pharmacokinetics properties of a test compound can help in the choice of a vehicle. 

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