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Biomedical subjects

A S White

Publications and source records attributed to A S White.

10 recordsLinked to original sources

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).

Adult

Pharmacokinetics of flupirtine in elderly volunteers and in patients with moderate renal impairment.

The pharmacokinetics of flupirtine after a single oral dose of 100mg have been studied in patients with moderate renal impairment and in healthy elderly subjects aged 66-83 years. Mean elimination half-life of flupirtine was higher in elderly patients than in younger normal subjects, and this was associated with an increased maximum serum concentration and reduced clearance. The mean half-life in patients with renal impairment was higher than in normal subjects. There was no correlation between observed elimination half-life and degree of renal impairment, but the creatinine clearance of most patients fell in a narrow range between 43 and 60 ml/min. In the light of these results and until further information is available, it would be prudent to start treatment of patients who are elderly or have evidence of renal impairment with half the dose of flupirtine recommended for younger patients with normal renal function.

Age Factors

The onset of seasonal quiescence in the female Bennett's wallaby (Macropus rufogriseus rufogriseus).

The breeding season of the non-lactating Bennett's wallaby terminates when animals enter the state of seasonal quiescence. To examine this transition, pouch young were removed from females at intervals which were 3, 4 or 8 weeks (6, 11 and 8 animals respectively) after the winter solstice. Within 48 days, 3, 1 and 1 females gave birth respectively, indicating that these animals were not in seasonal quiescence when pouch young were removed. Those animals which did not give birth were either in seasonal quiescence or had undergone a non-pregnant cycle. To differentiate between the 2 possibilities, techniques which would ensure the detection of pregnant and non-pregnant cycles were assessed in 8 females during the breeding season. As has been previously reported for the wallaby, changes in peripheral progesterone concentrations and the vaginal smear occurred during pregnant and non-pregnant reproductive cycles. In addition, mating was detected by marking the male with a mixture of coloured crayon and paraffin wax. It was concluded that reproductive cycles in female wallabies could be monitored by collecting blood samples 2 times each week for progesterone determination and daily examination of females for mating marks. These techniques were then used to study the onset of seasonal quiescence in 9 females. All animals continued to show reproductive cycles after the winter solstice and it was not until 10 weeks after the winter solstice that all animals were in seasonal quiescence. This represents an increase in the duration of the breeding season over that previously reported for this species.

Animals

Effects of lactation and season on plasma prolactin concentrations and response to bromocriptine during lactation in the Bennett's wallaby (Macropus rufogriseus rufogriseus).

Prolactin concentration was measured in plasma collected each week for 13 months from lactating and non-lactating Bennett's wallabies (Macropus rufogriseus rufogriseus). In non-lactating animals, prolactin concentrations decreased towards the end of the study but such changes did not appear to fit a seasonal pattern. Prolactin concentrations were low during early lactation and at a similar level to non-lactating animals, increased significantly during late pouch life (February-May), and then returned to non-lactating levels at a time coincident with permanent exit of the joey from the pouch. Temporary removal of joeys from their mothers in April was followed by a rapid decline in prolactin concentrations which remained low for 24 h until the joey was returned to its mother, whereupon prolactin concentrations increased significantly within 2 h. The effect of a single injection of bromocriptine (5 mg/kg) on lactation, embryonic diapause and plasma prolactin concentrations was examined at two stages of lactation. In November (lactational diapause), bromocriptine had no effect on prolactin concentrations but two out of four suckling joeys died on days 13 and 14 after treatment, and three out of four females gave birth on days 27, 27 and 28. Bromocriptine treatment in April (seasonal diapause) was followed by a significant reduction in prolactin concentrations and reduced growth rate of joeys belonging to treated females. New births were not observed. In view of the effect of bromocriptine on plasma prolactin concentrations in late lactation and the demonstration that domperidone (a dopamine antagonist) significantly increases plasma prolactin concentrations, it would seem that dopamine can act as a prolactin inhibitory hormone in this as in other mammalian species.

Animals