Respiratory and ventilatory effects of methadone in healthy women

The effects of oral methadone on respiration, ventilation, pupillary diameter, and plasma concentrations of estrone, estradiol, and progesterone were investigated in healthy nonpregnant women, 21 to 29 yr old. All women were in the follicular phase of the menstrual cycle. The study design was a randomized, double‐blind, placebo‐controlled trial. Six women received 15 mg methadone · HCl, and six received placebo. Alveolar ventilation and oxygen consumption before treatments correlated with plasma progesterone concentration (r 2 = 0.85 and 0.68) but the slope and x‐intercept of the ventilatory response to carbon dioxide curve did not. Female sex steroids in plasma were not affected by methadone. Mean elimination half‐life of methadone from serum was 19 hr. Methadone‐induced respiratory depression and miosis lasted more than 48 hr. The intensity of these changes was a linear function of the logarithm of the serum methadone concentration. Plasma progesterone concentration is an important determinant of resting ventilation and metabolism in the follicular phase of the menstrual cycle but endogenous progesterone does not protect women from the respiratory depressant effects of methadone. Clinical Pharmacology and Therapeutics (1981) 29, 373–380; doi: 10.1038/clpt.1981.51