Intraindividual variation in drug disposition

A. P. Alvares, A. Kappas, J. L. Eiseman, Karl Anderson, C. B. Pantuck, E. J. Pantuck, K. C. Hsiao, W. A. Garland, A. H. Conney

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Large interindividual differences occur in the in vivo metabolism of drugs due to genetic and environmental factors. Our studies show that intraindividual variabilities in rates of metabolism are relatively low for antipyrine and phenylbutazone, which are drugs that are primarily metabolized by the liver and have low hepatic extractions; whereas in the case of phenacetin, a drug that undergoes extensive metabolism in the gastrointestinal tract or during its first pass through the liver, or both, intraindividual variations in plasma half-lifes and areas under the plasma concentration-time curves are of much greater magnitude. In our studies, no effort was made to control the lifestyles of our subjects. The variations in rates of drug metabolism did not result from assay procedures, since there was little variation in measured concentrations when the drugs were added to plasma and assayed on multiple occasions. Intraindividual variation occurring in subjects given the drug on 5 different occasions may be due to changes in the external environment or changes in internal physiologic parameters or both. Our studies confirm the usefulness of antipyrine as a test drug in studying drug metabolism in man and also demonstrate that the antipyrine test may be able to detect those subjects whose environments are perturbed by unidentified factors.

Original languageEnglish (US)
Pages (from-to)407-419
Number of pages13
JournalClinical Pharmacology and Therapeutics
Volume26
Issue number4
StatePublished - Oct 1979
Externally publishedYes

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Antipyrine
Pharmaceutical Preparations
Liver
Phenacetin
Phenylbutazone
Half-Life
Gastrointestinal Tract
Life Style

ASJC Scopus subject areas

  • Pharmacology

Cite this

Alvares, A. P., Kappas, A., Eiseman, J. L., Anderson, K., Pantuck, C. B., Pantuck, E. J., ... Conney, A. H. (1979). Intraindividual variation in drug disposition. Clinical Pharmacology and Therapeutics, 26(4), 407-419.

Intraindividual variation in drug disposition. / Alvares, A. P.; Kappas, A.; Eiseman, J. L.; Anderson, Karl; Pantuck, C. B.; Pantuck, E. J.; Hsiao, K. C.; Garland, W. A.; Conney, A. H.

In: Clinical Pharmacology and Therapeutics, Vol. 26, No. 4, 10.1979, p. 407-419.

Research output: Contribution to journalArticle

Alvares, AP, Kappas, A, Eiseman, JL, Anderson, K, Pantuck, CB, Pantuck, EJ, Hsiao, KC, Garland, WA & Conney, AH 1979, 'Intraindividual variation in drug disposition', Clinical Pharmacology and Therapeutics, vol. 26, no. 4, pp. 407-419.
Alvares AP, Kappas A, Eiseman JL, Anderson K, Pantuck CB, Pantuck EJ et al. Intraindividual variation in drug disposition. Clinical Pharmacology and Therapeutics. 1979 Oct;26(4):407-419.
Alvares, A. P. ; Kappas, A. ; Eiseman, J. L. ; Anderson, Karl ; Pantuck, C. B. ; Pantuck, E. J. ; Hsiao, K. C. ; Garland, W. A. ; Conney, A. H. / Intraindividual variation in drug disposition. In: Clinical Pharmacology and Therapeutics. 1979 ; Vol. 26, No. 4. pp. 407-419.
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