Functional Assessment of Human Alcohol Dehydrogenase Family in Ethanol Metabolism: Significance of First-Pass Metabolism

Controversy exists concerning the site (stomach vs. liver) and magnitude of first-pass metabolism of ethanol. We quantitated gastric and total ethanol absorption rates in five male subjects and utilized these measurements to evaluate first-pass metabolism. Gastric emptying of ethanol (0.15 g/kg) was determined via a gamma camera and gastric absorption from the ratio of gastric ethanol to [14C]polyethylene glycol. Gastric absorption accounted for 30% and 10% of ethanol administered with food and water, respectively. With food, estimated gastric mucosal ethanol concentrations fell from 19 to 5 mM over 2 h. Calculations using these concentrations and kinetic data for gastric alcohol dehydrogenase showed <2% of the dose underwent gastric metabolism. Application of observed ethanol absorption rates to a model of human hepatic ethanol metabolism indicated that only 30% and 4% of the dose underwent first-pass metabolism when administered with food and water, respectively. We conclude that virtually all first-pass ethanol metabolism occurs in the liver and first-pass metabolism accounts for only a small fraction of total clearance.

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Helicobacter pylori Infection Decreases Gastric Alcohol Dehydrogenase Activity and First-Pass Metabolism of Ethanol in Man

Digestion ◽

10.1159/000007508 ◽

1998 ◽

Vol 59 (4) ◽

pp. 314-320 ◽

Cited By ~ 25

Author(s):

Ulrich A. Simanowski ◽

Gerlinde Egerer ◽

Carl Oneta ◽

Thomas Keil ◽

Xavier Parés ◽

...

Keyword(s):

Helicobacter Pylori ◽

Alcohol Dehydrogenase ◽

Dehydrogenase Activity ◽

Alcohol Dehydrogenase Activity ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism ◽

Gastric Alcohol Dehydrogenase

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Helicobacter pylori eradication increases gastric alcohol dehydrogenase activity but does not affect ethanol first pass metabolism

Gastroenterology ◽

10.1016/s0016-5085(98)80337-5 ◽

1998 ◽

Vol 114 ◽

pp. A84 ◽

Cited By ~ 1

Author(s):

S Campbell ◽

A Fletcher ◽

EC Graham ◽

W Borland ◽

MEJ Lean ◽

...

Keyword(s):

Helicobacter Pylori ◽

Alcohol Dehydrogenase ◽

Dehydrogenase Activity ◽

Helicobacter Pylori Eradication ◽

Alcohol Dehydrogenase Activity ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism ◽

Gastric Alcohol Dehydrogenase

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Can the liver account for first-pass metabolism of ethanol in the rat?

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1994.267.3.g452 ◽

1994 ◽

Vol 267 (3) ◽

pp. G452-G457

Author(s):

M. D. Levitt ◽

D. G. Levitt ◽

J. Furne ◽

E. G. DeMaster

Keyword(s):

Gastric Mucosa ◽

Alcohol Dehydrogenase ◽

Portal Vein ◽

Absorption Rate ◽

Blood Alcohol ◽

Experimental Animals ◽

First Pass Metabolism ◽

First Pass ◽

Kinetics Of ◽

Pass Metabolism

Although the liver has far more ethanol-metabolizing capacity than does the stomach, all first-pass metabolism of alcohol is said to occur in the gastric mucosa because hepatic alcohol dehydrogenase is saturated at low peripheral blood alcohol concentrations. We evaluated the ability of the liver to carry out first-pass metabolism in the rat by constructing a model of hepatic handling of ethanol based on the kinetics of ethanol clearance after intraperitoneal injection of alcohol. Because the efficiency of first-pass metabolism is influenced by the rate of delivery of ethanol, the absorption rate of oral alcohol (0.5 g/kg) was determined and applied to the model. The blood ethanol curves predicted by the model for ethanol delivered via the portal vein or via intravenous infusion were virtually identical to the ethanol curves observed in experimental animals with each of these routes of delivery. We conclude that the liver can account for all first-pass metabolism experimentally observed in the rat, and it is not necessary to postulate some extrahepatic site of first-pass metabolism, such as the stomach.

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Zinc Administration Improves Gastric Alcohol Dehydrogenase Activity and First-Pass Metabolism of Ethanol in Alcohol-Fed Rats

Alcoholism Clinical and Experimental Research ◽

10.1111/j.1530-0277.1997.tb04498.x ◽

1997 ◽

Vol 21 (9) ◽

pp. 1619-1622 ◽

Cited By ~ 7

Author(s):

Joan Caballeria ◽

America Gimenez ◽

Hernan Andreu ◽

Ramon Deulofeu ◽

Albert Pares ◽

...

Keyword(s):

Alcohol Dehydrogenase ◽

Dehydrogenase Activity ◽

Alcohol Dehydrogenase Activity ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism ◽

Gastric Alcohol Dehydrogenase

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Identification of a Cranberry Juice Product Capable of Inhibiting Enteric CYP3A-Mediated First-Pass Metabolism in Humans

Planta Medica ◽

10.1055/s-2008-1075176 ◽

2008 ◽

Vol 74 (03) ◽

Author(s):

N Ngo ◽

Z Yan ◽

TN Graf ◽

DR Carrizosa ◽

EC Dees ◽

...

Keyword(s):

Cranberry Juice ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism

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Development, Characterization and Optimization of Mucoadhesive Tablet for Buccal Delivery of Domperidone

Drug Delivery Letters ◽

10.2174/2210303108666181108120840 ◽

2019 ◽

Vol 9 (1) ◽

pp. 37-49

Author(s):

Jagdale Sachin ◽

Panbude Aishwarya ◽

Navasare Priya

Keyword(s):

Drug Release ◽

Factorial Design ◽

Research Work ◽

Wet Granulation ◽

Buccal Delivery ◽

Scanning Calorimetry ◽

Mucoadhesive Polymers ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism

Background and Objective: Upon oral administration domeperidone is rapidly absorbed, but subjected to the first pass effect which lowers systemic bioavailability to 15%. Mucoadhesive tablet can remain attached to buccal mucosa and becomes capable of bypassing hepatic first-pass metabolism to improve absorption directly into systemic circulation. The present research work was carried with an aim to develop, evaluate and optimize mucoadhesive tablet containing domperidone (DOME) for buccal delivery using different bio-adhesive polymeric combinations. </P><P> Methods: The buccal tablets were formulated by wet granulation method using isopropyl alcohol. The preliminary formulations were prepared using combinations of HPMC K4, HPMC K15, HPMC K100, HPMC E5 as mucoadhesive polymers. 32 full factorial design was applied to determine the effect of independent variables like concentration of mucoadhesive polymers (HPMC K15 and HPMC K100) over dependent variables like mucoadhesive properties (swelling index, bioadhesive strength and in vitro drug release). The prepared mucoadhesive tablets were evaluated for their tablet properties and mucoadhesive properties. The interactions between drug and polymers were studied by Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). </P><P> Results: All formulations of factorial design showed satisfactory physicochemical, mechanical and bioadhesive characteristics. The formulation F9 exhibited maximum cumulative drug release, mucoadhesive strength and swelling index. Conclusion: The developed buccal tablet of domperidone might prove alternative to bypass the hepatic first pass metabolism and to avoid degradation which in turn may result in reducing the frequency of administration. Thus, mucoadhesive tablet of domeperidone may become viable alternative overcoming the side effects; achieving greater therapeutic effectiveness and improving the patient compliance.

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