Abstract
1. The pharmacokinetics of dextropropoxyphene (D) and nordextropropoxyphene (ND) have been studied in 12 healthy young (21-28 years) and 12 healthy elderly (70-79 years) male and female subjects. Each received 65 mg D and plasma D and ND concentrations were measured by h.p.l.c. with electrochemical detection for up to 7 days and again after 65 mg D, 3 times daily for 1 week. 2. There were no significant differences in median D and ND half-life, AUC, Cmax and tmax between the male and female subjects in either group. Within the groups the mean D half-life (h) was longer in the young after multiple dosing (mean +/- s.d.:13.2 +/- 5.2 and 23.7 +/- 11.3, P less than 0.05, paired t-test) but there were no other significant differences. 3. Between the groups, the median single and multiple dose D and ND half-lives were all significantly longer (P less than 0.02) and the median D AUC for both single and multiple doses was significantly higher (P less than 0.01 and P less than 0.05, respectively, Mann-Whitney U-tests) in the elderly. 4. There was no relation between multiple dose Cmax and other parameters such as single dose D half-life. However, across the groups D and ND half-lives after both single and multiple dosage correlated significantly with estimated creatinine clearance, the correlation being strongest with ND (r = -0.76 and -0.84, respectively).
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Selected References
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- Abernethy D. R., Greenblatt D. J. Impairment of lidocaine clearance in elderly male subjects. J Cardiovasc Pharmacol. 1983 Nov-Dec;5(6):1093–1096. doi: 10.1097/00005344-198311000-00027. [DOI] [PubMed] [Google Scholar]
- Abernethy D. R., Greenblatt D. J., Shader R. I. Imipramine and desipramine disposition in the elderly. J Pharmacol Exp Ther. 1985 Jan;232(1):183–188. [PubMed] [Google Scholar]
- Antal E. J., Kramer P. A., Mercik S. A., Chapron D. J., Lawson I. R. Theophylline pharmacokinetics in advanced age. Br J Clin Pharmacol. 1981 Nov;12(5):637–645. doi: 10.1111/j.1365-2125.1981.tb01282.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cockcroft D. W., Gault M. H. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. doi: 10.1159/000180580. [DOI] [PubMed] [Google Scholar]
- Crome P., Gain R., Ghurye R., Flanagan R. J. Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in elderly hospital patients after single and multiple doses of distalgesic. Preliminary analysis of results. Hum Toxicol. 1984 Aug;3 (Suppl):41S–48S. doi: 10.1177/096032718400300105. [DOI] [PubMed] [Google Scholar]
- Dawling S. Monitoring of tricyclic antidepressant therapy. Clin Biochem. 1982 Feb;15(1):56–61. doi: 10.1016/s0009-9120(82)90511-2. [DOI] [PubMed] [Google Scholar]
- Flanagan R. J., Ramsey J. D., Jane I. Measurement of dextropropoxyphene and nordextropropoxyphene in biological fluids. Hum Toxicol. 1984 Aug;3 (Suppl):103S–114S. doi: 10.1177/096032718400300112. [DOI] [PubMed] [Google Scholar]
- Gram L. F., Schou J., Way W. L., Heltberg J., Bodin N. O. d-Propoxyphene kinetics after single oral and intravenous doses in man. Clin Pharmacol Ther. 1979 Oct;26(4):473–482. doi: 10.1002/cpt1979264473. [DOI] [PubMed] [Google Scholar]
- Greenblatt D. J., Abernethy D. R., Locniskar A., Harmatz J. S., Limjuco R. A., Shader R. I. Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology. 1984 Jul;61(1):27–35. [PubMed] [Google Scholar]
- Greenblatt D. J., Abernethy D. R., Shader R. I. Pharmacokinetic aspects of drug therapy in the elderly. Ther Drug Monit. 1986;8(3):249–255. doi: 10.1097/00007691-198609000-00001. [DOI] [PubMed] [Google Scholar]
- Greenblatt D. J., Divoll M., Abernethy D. R., Moschitto L. J., Smith R. B., Shader R. I. Reduced clearance of triazolam in old age: relation to antipyrine oxidizing capacity. Br J Clin Pharmacol. 1983 Mar;15(3):303–309. doi: 10.1111/j.1365-2125.1983.tb01503.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inturrisi C. E., Colburn W. A., Verebey K., Dayton H. E., Woody G. E., O'Brien C. P. Propoxyphene and norpropoxyphene kinetics after single and repeated doses of propoxyphene. Clin Pharmacol Ther. 1982 Feb;31(2):157–167. doi: 10.1038/clpt.1982.25. [DOI] [PubMed] [Google Scholar]
- Johnston A., Woollard R. C. STRIPE: an interactive computer program for the analysis of drug pharmacokinetics. J Pharmacol Methods. 1983 May;9(3):193–199. doi: 10.1016/0160-5402(83)90038-4. [DOI] [PubMed] [Google Scholar]
- Lawson A. A., Northridge D. B. Dextropropoxyphene overdose. Epidemiology, clinical presentation and management. Med Toxicol Adverse Drug Exp. 1987 Nov-Dec;2(6):430–444. doi: 10.1007/BF03259877. [DOI] [PubMed] [Google Scholar]
- Nickander R. C., Emmerson J. L., Hynes M. D., Steinberg M. I., Sullivan H. R. Pharmacologic and toxic effects in animals of dextropropoxyphene and its major metabolite norpropoxyphene: a review. Hum Toxicol. 1984 Aug;3 (Suppl):13S–36S. doi: 10.1177/096032718400300103. [DOI] [PubMed] [Google Scholar]
- Perrier D., Gibaldi M. Influence of first-pass effect on the systemic availability of propoxyphene. J Clin Pharmacol New Drugs. 1972 Nov-Dec;12(11):449–452. doi: 10.1002/j.1552-4604.1972.tb00245.x. [DOI] [PubMed] [Google Scholar]
- Roberts I., Flanagan R. J., Strang J., Prescott L. F. Toxicological studies in a Distalgesic addict. Hum Toxicol. 1986 May;5(3):207–210. doi: 10.1177/096032718600500310. [DOI] [PubMed] [Google Scholar]
- Schou J., Angelo H., Dam W., Jensen K., Christensen J. M. Pharmacokinetics of dextropropoxyphene in acute poisoning. Arch Toxicol Suppl. 1978;(1):343–346. doi: 10.1007/978-3-642-66896-8_73. [DOI] [PubMed] [Google Scholar]
- Verebely K., Inturrisi C. E. Disposition of propoxyphene and norpropoxyphene in man after a single oral dose. Clin Pharmacol Ther. 1974 Mar;15(3):302–309. doi: 10.1002/cpt1974153302. [DOI] [PubMed] [Google Scholar]
- Wagner J. G., Welling P. G., Sedman A. J. Plasma concentrations of propoxyphene in man. II. Pharmacokinetics. Int Z Klin Pharmakol Ther Toxikol. 1972 Feb;5(4):381–388. [PubMed] [Google Scholar]
- Wolen R. L., Gruber C. M., Jr, Kiplinger G. F., Scholz N. E. Concentration of propoxyphene in human plasma following oral, intramuscular, and intravenous administration. Toxicol Appl Pharmacol. 1971 Jul;19(3):480–492. doi: 10.1016/0041-008x(71)90006-8. [DOI] [PubMed] [Google Scholar]
- Wolen R. L., Ziege E. A., Gruber C. M., Jr Determination of propoxyphene and norpropoxyphene by chemical ionization mass fragmentography. Clin Pharmacol Ther. 1975 Jan;17(1):15–20. doi: 10.1002/cpt197517115. [DOI] [PubMed] [Google Scholar]