A review of the clinical pharmacokinetics and metabolism of the alpha 1-adrenoceptor antagonist indoramin

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
D M Pierce

Abstract

1. The alpha 1-adrenoceptor antagonist indoramin is rapidly and extensively absorbed after oral administration, but with only low to moderate bioavailability (8-24% median) from the tablet (Baratol). Although plasma protein binding is high (72-86%), the drug is widely distributed into tissues (with median Vz 6.3-7.7 l/kg after i.v. dosage). 2. Elimination of indoramin is rapid in most healthy volunteers, with median plasma clearances of 18-26 ml/min per kg, after i.v. dosage. Elimination occurs principally by metabolism, the major route being indole 6-hydroxylation, followed by sulphate conjugation of 6-hydroxyindoramin. The faecal route of excretion predominates (45-50% of dose), with a further 35-40% in the urine. 3. Extensive variation in single-dose oral pharmacokinetics of indoramin is due largely to the existence of a poor metabolizer phenotype which co-segregates with that of debrisoquine. 4. On repeated administration (37.5 mg twice daily) to healthy volunteers, plasma concentrations of indoramin accumulate 3-4-fold above those anticipated from single-dose kinetics. However, steady state is achieved within the first week of dosing. 5. The pharmacokinetics of indoramin are substantially altered in the elderly. The oral A...Continue Reading

References

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