Metabolism and pharmacokinetics of orciprenaline in various animal species and man.

The physiological disposition of tritiated orciprenaline, the 3,5-dihydroxy-isomer of isoprenaline, has been studied in rat, rabbit, cat and man. In the lungs, liver and kidneys of the rat higher 3H-concentrations were found than in the plasma after i.v. injection. A higher percentage of unchanged drug was located in the heart, lungs and skeletal muscle only. In the plasma of rabbit and cat as well as man the decline of 3H-activity was biphasic after i.v. administration with a half-life of 15 hr in the rabbit 6 hr in cat and man for the slower phase. The pharmacokinetic analysis of the post-infusion data in man resulted in an open two-compartment model with a high volume of distribution (ca. 700 liters). The total clearance (1400 ml/min) was rather high. The renal clearance contributed to 10 per cent only. The amount of drug absorbed after oral administration amounted to 44%, the reduced biovailability of 10 per cent indicated a fist-pass effect. The metabolism lead only to conjugates with glucuronic acid, most probably at one of the phenolic hydroxyl groups in rat, rabbit and man. The cat did not metabolize orciprenaline to an appreciable amount.