Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in young and elderly volunteers after single and multiple dextropropoxyphene dosage.
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).
Flanagan
R J
RJ
Poisons Unit, Guy's Hospital, London.
Johnston
A
A
White
A S
AS
Crome
P
P
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D011431:Dextropropoxyphene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male
C002756:norpropoxyphene; D011431:Dextropropoxyphene