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Drug pharmacokinetics and the carbon dioxide breath test

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Abstract

The interrelationship of the pharmacokinetics of a drug and the expiration of carbon dioxide formed as a metabolite have been studied. The pharmacokinetic characteristics of the drug that affect the usefulness of the carbon dioxide excretion as a measure of liver function were examined by means of computer simulations. The parent drug extraction ratio, fraction demethylated, volume of distribution, and absorption rate of an oral dosage form all contribute to the carbon dioxide breath test result. A drug that would be a useful substrate when the carbon dioxide breath test is used as a probe for changes in liver function should be at least 50% metabolized by demethylation, have a hepatic extraction ratio of 0.2–0.5, and be administered in a form that is rapidly absorbed.

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Abbreviations

CL c :

net clearance of formaldehyde to carbon dioxide

CL int,f :

intrinsic hepatic clearance of formation of formaldehyde from parent drug (bound and unbound to plasma proteins)

CL int,p :

intrinsic hepatic clearance of total parent drug (bound and unbound to plasma proteins)

CL sys,f :

systemic hepatic clearance of formation of formaldehyde from parent drug,Q H CL int,f /(Q H +CL int,p )

CL sys,p :

systemic hepatic clearance of parent drug,Q H CL int,p /(Q H +CL int,p )

E:

extraction ratio,CL int,p /(Q H +CL int,p

F I-E:

fraction escaping first-pass metabolism,Q H/(Q H +CL int,p

fm :

fraction of parent drug metabolized by demethylation to formaldehyde,CL int,f /CL int,p

HCHO :

amount of formaldehyde

[HCHO]:

concentration of formaldehyde

κ a :

absorption rate constant

M i :

metabolite of P formed by routes other than demethylation

M 1 :

metabolite of P formed by demethylation

P :

amount of parent drug in the body

[P]:

concentration of parent drug measured in arterial blood

P A :

amount of parent drug at absorption site

P L :

amount of parent drug in the liver

Q H :

hepatic blood flow

V F :

volume of distribution of formaldehyde

V p :

volume of distribution of parent drug

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  1. Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, 20205-1000, Washington, D.C.

    Elizabeth A. Lane & Ioanis Parashos

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  1. Elizabeth A. Lane
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Lane, E.A., Parashos, I. Drug pharmacokinetics and the carbon dioxide breath test. Journal of Pharmacokinetics and Biopharmaceutics 14, 29–49 (1986). https://doi.org/10.1007/BF01059282

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  • DOI: https://doi.org/10.1007/BF01059282

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