Premium
Propoxyphene and norpropoxyphene kinetics after single and repeated doses of propoxyphene
Author(s) -
Inturrisi Charles E,
Colburn Wayne A,
Verebey Karl,
Dayton Harry E,
Woody George E,
P O'Brien Charles
Publication year - 1982
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1982.25
Subject(s) - propoxyphene , pharmacokinetics , dosing , chemistry , pharmacology , metabolite , kinetics , half life , medicine , analgesic , biochemistry , physics , quantum mechanics
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 informer 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 210 ml/min, P half‐life (t½) increased from 3.3 to 11.8 hr, NP t½ 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. Clinical Pharmacology and Therapeutics (1982) 31 , 157–167; doi: 10.1038/clpt.1982.25