European Journal of Clinical Pharmacology

, Volume 35, Issue 1, pp 109–111 | Cite as

Therapeutic doses of codeine have no effect on acetaminophen clearance or metabolism

  • J. Sonne
  • H. Enghusen Poulsen
  • S. Loft
  • M. Døssing
  • A. Vollmer-Larsen
  • K. Simonsen
  • H. Thyssen
  • K. Lundstrøm
Short Communications

Summary

In nine healthy volunteers, the clearance and metabolism of acetaminophen 1000 mg i.v. was evaluated with and without two concomitant oral doses of codeine in order to investigate a possible interaction. Plasma acetaminophen was followed for 720 min and urine was collected for 24 h after each dose for determination of metabolites.

When codeine was coadministered, the average total clearance of acetaminophen and its clearance by glucuronidation, sulphation and mercapturate formation were 0.58 to 1.12-times the control values.

It is concluded that therapeutic doses of codeine do not influence the clearance or metabolism of acetaminophen.

Key words

acetaminophen codeine clearance metabolite formation glucuronidation pharmacokinetics healthy volunteers drug interaction 

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References

  1. 1.
    Quiding H, Persson G, Ahlström U, Bångens S, Hellem S, Johansson G, Jönsson E, Nordh PG (1982) Paracetamol plus supplementary doses of codeine. An analgesic study of repeated doses. Eur J Clin Pharmacol 23: 315–319Google Scholar
  2. 2.
    Ahlström U, Fåhraeus J, Quiding H, Ström C (1985) Multiple doses of paracetamol plus codeine taken immediately after oral surgery. Eur J Clin Pharmacol 27: 693–696Google Scholar
  3. 3.
    Prescott LF (1980) Kinetics and metabolism of paracetamol and phenacetin. Br J Clin Pharmacol 10: 291S-298SGoogle Scholar
  4. 4.
    Adler TK, Fujimoto JM, Way EL, Baker EM (1955) The metabolic fate of codeine in man. J Pharmacol Exp Ther 114: 251–262Google Scholar
  5. 5.
    Findlay JWA, Jones EC, Buth RF, Welch RM (1978) Plasma codeine and morphine concentrations after therapeutical oral doses of codeine-containing analgesics. Clin Pharmacol Ther 24: 60–68Google Scholar
  6. 6.
    Poulsen HE, Lerche A, Pedersen NT (1985) Phenobarbital induction does not potentiate hepatotoxicity but accelerates liver cell necrosis from acetaminophen overdose in the rat. Pharmacology 30: 100–108Google Scholar
  7. 7.
    Moldeus P (1978) Paracetamol metabolism and toxicity in isolated hepatocytes from rat and mouse. Biochem Pharmacol 27: 2859–2863Google Scholar
  8. 8.
    Sonne J, Poulsen HE, Andreasen PB (1986) Single dose oxazepam has no effect on acetaminophen clearance or metabolism. Eur J Clin Pharmacol 30: 127–129Google Scholar
  9. 9.
    Brown DR, Manno JE (1978) ESTRIP, a BASIC computer program for obtaining initial polyexponential parameter estimates. J Pharm Sci 67: 1687–1691Google Scholar
  10. 10.
    Levy G, Yamada H (1971) Drug biotransformation interactions in man III. Acetaminophen and salicylamide. J Pharm Sci 60: 215–221Google Scholar
  11. 11.
    Bolanaowska W, Gessner T (1978) Drug interactions: Inhibition of acetaminophen glucuronidation by drugs. J Pharmacol Exp Ther 206: 233–238Google Scholar
  12. 12.
    Dybing E (1976) Inhibition of acetaminophen glucuronidation by oxazepam. Biochem Pharmacol 25: 1421–1425Google Scholar
  13. 13.
    Douidar SM, Ahmed AE (1987) A novel mechanism for the enhancement of acetaminophen hepatotoxicity by phenobarbital. J Pharmacol Exp Ther 240: 578–583Google Scholar
  14. 14.
    Watkins JB, Gregus Z, Thompson TN, Klaassen CD (1982) Induction studies on the functional heterogeneity of rat liver UDP-glucuronosyltransferases. Toxicol Appl Pharmacol 64: 439–446Google Scholar
  15. 15.
    Roy Chowdhury J, Roy Chowdhury N, Falany CN, Tephly TR, Arias IM (1986) Isolation and characterization of multiple forms of rat liver UDP-glucuronate glucuronosyltransferase. Biochem J 233: 827–837Google Scholar
  16. 16.
    Bock KW, Wiltfang J, Blume R, Ullrich D, Bircher J (1987) Paracetamol as a test drug to determine glucuronide formation in man. Effects of inducers and of smoking. Eur J Clin Pharmacol 31: 677–683Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • J. Sonne
    • 1
  • H. Enghusen Poulsen
    • 2
  • S. Loft
    • 3
  • M. Døssing
    • 4
  • A. Vollmer-Larsen
    • 1
  • K. Simonsen
    • 4
  • H. Thyssen
    • 1
  • K. Lundstrøm
    • 1
  1. 1.Department of Medicine FGentofte University HospitalCopenhagenDenmark
  2. 2.Department of Medicine ARigshospitaletCopenhagenDenmark
  3. 3.Department of PharmacologyUniversity of CopenhagenCopenhagenDenmark
  4. 4.Department of Medicine PBispebjerg University HospitalCopenhagenDenmark

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