Journal of Pharmacokinetics and Biopharmaceutics

, Volume 14, Issue 1, pp 29–49

Drug pharmacokinetics and the carbon dioxide breath test

  • Elizabeth A. Lane
  • Ioanis Parashos
Article

DOI: 10.1007/BF01059282

Cite this article as:
Lane, E.A. & Parashos, I. Journal of Pharmacokinetics and Biopharmaceutics (1986) 14: 29. doi:10.1007/BF01059282

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.

Key words

carbon dioxide breath test pharmacokinetics metabolite extraction ratio aminopyrine caffeine 

Appendix b. symbols

CLc

net clearance of formaldehyde to carbon dioxide

CLint,f

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

CLint,p

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

CLsys,f

systemic hepatic clearance of formation of formaldehyde from parent drug,QHCLint,f/(QH +CLint,p)

CLsys,p

systemic hepatic clearance of parent drug,QHCLint,p/(QH +CLint,p)

E

extraction ratio,CLint,p/(QH +CLint,p

F I-E

fraction escaping first-pass metabolism,QH/(QH +CLint,p

fm

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

HCHO

amount of formaldehyde

[HCHO]

concentration of formaldehyde

κa

absorption rate constant

Mi

metabolite of P formed by routes other than demethylation

M1

metabolite of P formed by demethylation

P

amount of parent drug in the body

[P]

concentration of parent drug measured in arterial blood

PA

amount of parent drug at absorption site

PL

amount of parent drug in the liver

QH

hepatic blood flow

VF

volume of distribution of formaldehyde

Vp

volume of distribution of parent drug

Copyright information

© Plenum Publishing Corporation 1986

Authors and Affiliations

  • Elizabeth A. Lane
    • 1
  • Ioanis Parashos
    • 1
  1. 1.Laboratory of Clinical Studies, DICBRNational Institute on Alcohol Abuse and AlcoholismWashington, D.C.

Personalised recommendations