CF4 4XN and 'Wyeth Research (UK), Taplow, Maidenhead, Berkshire, UK 1 The respiratory and psychomotor effects of a single oral dose of meptazinol (200 mg) and dextropropoxyphene (65 mg)/paracetamol (650 mg) mixture, was compared alone and in combination with ethanol (0.8 g kg-').2 Peak saccade velocity following meptazinol or the dextropropoxyphene/paracetamol mixture was not significantly different from placebo. When each of the treatments was followed by ethanol administration, a significant decrease in saccade velocity (P < 0.01) was seen. 3 Given alone, neither of the analgesic drugs produced a significant change in the slope of the ventilatory response to hypercapnia. Ethanol did not affect the ventilatory response to hypercapnia when given alone or in combination with meptazinol, but when given with the dextropropoxyphene/paracetamol mixture, a significant reduction in the slope of the ventilatory response to hypercapnia occurred at 1.5 h (P < 0.05) and 2 h (P < 0.01) after administration of the analgesic drug. 4 No pharmacokinetic interaction was demonstrated between ethanol and meptazinol or the dextropropoxyphene/paracetamol mixture in the doses used. 5 In contrast to meptazinol, the dextropropoxyphene/paracetamol mixture interacts with ethanol on the ventilatory function.

Oral administration of meptazinol (200 mg Meptid) to male and female geriatric patients (greater than 70 years) resulted in rapid absorption, with peak drug concentrations at 0.5 to 3 h after dosage. Subsequent elimination also proceeded rapidly with a half-life of 3.39 h (+/- 0.26 SEM) after a single dose and 4.97 h (+/- 0.80 SEM) after 13 consecutive 6-h doses. These values were not statistically different. There was no accumulation of meptazinol above that expected from the single-dose kinetics. Plasma protein binding of meptazinol was 33.8% (+/- 0.74 SEM). No sex difference was apparent in any of the pharmacokinetic parameters determined. Comparison of these results with those obtained in an earlier study in young volunteers showed that although the half-life of meptazinol was somewhat longer than the value of 2 h seen in the young, peak plasma concentrations after single and multiple dosing were similar for both age groups, implying that clearance remained largely unaltered. It was concluded that there was no pharmacokinetic basis for recommending a reduction in dosage when treating elderly patients with oral meptazinol.

The pharmacokinetics of meptazinol (Meptid) have been studied in nine male volunteers after single and multiple oral administration of 200 mg tablets and also after a single 25 mg intravenous dose. Plasma concentrations of meptazinol were determined by HPLC using fluorescence detection. Drug absorption after oral dosage was rapid, peak plasma concentrations being reached between 0.25 and 2 h after drug administration. Subsequent elimination proceeded in an apparently mono-exponential fashion with a half-life of 2 h, although after intravenous dosage there was evidence of an initial rapid distributive phase. The mean total plasma clearance was 2.21/min and the mean apparent volume of distribution (Vd beta) was 4.99 l/min. The bioavailability ranged from 1.9 to 18.5% (mean = 8.7%) and was related to the rate of absorption. Multiple dosing, 6-hourly for 3 days, did not produce any accumulation above that predicted from a single dose. Plasma protein binding of the drug was 27.1% and did not vary over the therapeutic concentration range of 25 to 250 ng/ml.

We have determined the pharmacokinetics of meptazinol after its intravenous and intramuscular administration in a crossover study in 7 elderly hospital in-patients (greater than 70 years), and have compared with the results from 14 healthy, young volunteers (ages 20-40 years). The systemic availability after i.m. administration was comparable to that after i.v. administration, a result consistent with the physicochemical properties of the drug. There was a slight, but statistically significant (p less than 0.01) prolongation in t1/2Z in the elderly (mean 2.93 h) compared with the young (mean 2.06 h). This was associated with a 25% lower clearance in the elderly rather than with any alteration in volume of distribution. However, these changes would not appear to be substantial enough to require a revised dosage recommendation for meptazinol for this age group.

We have studied the disposition of the centrally-acting analgesic meptazinol in a group of age-matched non-pregnant and pregnant (36-38 weeks gestation) women. Ten non-pregnant and nine multiparous pregnant volunteers each received a single i.v. dose of meptazinol hydrochloride (equivalent to 25 mg base). A further group of 9 non-pregnant (including four of the original participants) and 10 multiparous pregnant subjects were given repeated i.v. doses of meptazinol hydrochloride (each equivalent to 10 mg base) at 30-min intervals for 2.5 h. Meptazinol plasma concentrations were determined by HPLC using fluorescence detection and the pharmacokinetic variables investigated. After single dosing there were no statistical differences in half-life, clearance, or apparent volume of distribution between the two groups, suggesting that the disposition of meptazinol was not altered by pregnancy. This was confirmed in the repeated dose study, in which no significant differences occurred in either the plasma concentrations achieved or in areas under the curves between the non-pregnant and pregnant subjects. Furthermore, the steady-state concentrations were comparable with those predicted from the single dose results. This indicates that there should be no requirement for dosage alteration of meptazinol during pregnancy.