Propoxyphene and norpropoxyphene kinetics after single and repeated doses of propoxyphene

Clin Pharmacol Ther. 1982 Feb;31(2):157-67. doi: 10.1038/clpt.1982.25.


Plasma concentrations of propoxyphene (P) and its pharmacologically active metabolite norpropoxyphene (NP) were determined in normal subjects after single 130-mg oral doses and during and after 13 consecutive oral doses of 130 mg P, and in former heroin addicts who were maintained on 900 to 1200 mg of P per day. The data were analyzed using a first-pass elimination pharmacokinetic model. Both P and NP cumulated during repeated dosing to levels 5 to 7 times those after the first dose. In contrast, "maintenance" patients exhibited steady-state trough plasma NP cumulation that exceeded that of P by a factor of 13. Several changes in P and NP kinetics occurred during repeated dosing with P to the normal subjects: P clearance decreased from 994 to 508 ml/min, NP clearance decreased from 454 to 2210 ml/min, P half-life (t 1/2) increased from 3.3 to 11.8 hr, NP t 1/2 increased from 6.1 to 39.2 hr, and area under the concentration time curves for P and NP were doubled. These changes in kinetics during repeated dosing resulted in more extensive cumulation of P and NP than would be predicted from the single-dose kinetic profile. Changes in the extent of first-pass elimination of P result in variability in plasma P and NP that may contribute to P-induced toxicity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Dextropropoxyphene / analogs & derivatives*
  • Dextropropoxyphene / metabolism*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Kinetics
  • Male
  • Mathematics
  • Models, Biological


  • norpropoxyphene
  • Dextropropoxyphene