Summary
Data from a previously published single dose study of d-propoxyphene 65 mg given i.v. to 8 healthy subjects have been subjected to non linear regression analysis by a curve-fitting program to test the applicability of a 2- and a 3-compartment open model. Analysis of residuals (difference between observed and computed concentrations) revealed similar systematic deviations in all 8 subjects when the 2-compartment model was used (5–10 h negative residuals, after 13 h positive residuals). In contrast, curve-fit by a 3-compartment model (with two parallel peripheral compartments) was good with no systematic deviations. The data show that a terminal monoexponential decline in d-propoxyphene concentrations cannot be expected until 15–30 h after single dose administration, and that the determination of the corresponding half-life is rather inaccurate. Accordingly, precise steady state level predictions may be difficult to obtain from conventional single dose studies with d-propoxyphene.
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Gram, L.F., Schmidt, K., Christensen, F.N. et al. D-propoxyphene kinetics in man: Significance of a deep third compartment. Eur J Clin Pharmacol 26, 749–752 (1984). https://doi.org/10.1007/BF00541937
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DOI: https://doi.org/10.1007/BF00541937