Pharmacokinetics of promethazine and its sulphoxide metabolite after intravenous and oral administration to man

Br J Clin Pharmacol. 1983 Mar;15(3):287-93. doi: 10.1111/j.1365-2125.1983.tb01501.x.

Abstract

Blood concentrations of promethazine and promethazine sulphoxide have been measured following oral and intravenous administration of promethazine to seven healthy male volunteers. Promethazine disposition is characterised by a large volume of distribution (1970 1) and a high blood clearance (1.141 min-1). Less than 1% of the dose is excreted unchanged in the urine, therefore total body clearance is essentially metabolic clearance. In accord with this high clearance the oral availability of promethazine is only 25%. The absorption of promethazine from the gastrointestinal tract exceeds 80% in most subjects. Minimal metabolism by the gastrointestinal mucosa is implicated. Promethazine sulphoxide pharmacokinetics are consistent with a pronounced first pass effect. Although the area under the curve for this metabolite is not route dependent, there is a marked alteration in the shape of the metabolite curve when oral and intravenous data are compared. Evidence is presented to support the hypothesis that S-oxidation of promethazine is predominantly an hepatic event. The conclusions of previous investigators with regard to the role of the gut mucosa in S-oxidation of phenothiazines is critically assessed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Half-Life
  • Humans
  • Injections, Intravenous
  • Kinetics
  • Male
  • Promethazine / administration & dosage
  • Promethazine / blood
  • Promethazine / metabolism*

Substances

  • Promethazine