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

Abstract

1 Blood concentrations of promethazine and promethazine sulphoxide have been measured following oral and intravenous administration of promethazine to seven healthy male volunteers. 2 Promethazine disposition is characterised by a large volume of distribution (1970 1) and a high blood clearance (1.141 min-'). 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. 3 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.

Oral premedication for the prevention of hypersensitivity reactions to paclitaxel

“…It is used for the treatment of allergic conditions but it has also antiemetic effect. After oral or intramuscular administration, peak plasma concentration was observed for 2-3 h [15]. Promethazine undergoes extensive metabolism, predominantly to promethazine sulfoxide and to N-desmethylpromethazine.…”

Drug metabolite concentration‐time profiles: influence of route of drug administration.

“…Other examples of highly cleared drugs whose metabolite concentration-time profiles show route dependence include nortriptyline (Alvan et al, 1977), amitriptyline (Mellstrom et al, 1982), imipramine (Gram & Christiansen, 1975) and promethazine (Taylor et al, 1983). However, the degree to which these drugs' metabolites show the biphasic metabolite decline is variable.…”

“…If renal excretion is responsible for the elimination of more than 10% of the drug dose then the AUC(m) may show appreciable route dependence. Examples of metabolites where AUC (m) is not route dependent include 10-hydroxynortriptyline following nortriptyline administration (Alvan et al, 1977), nortriptyline following amitriptyline administration (Mellstrom et al, 1982) and promethazine sulphoxide (Taylor et al, 1983) following promethazine administration.…”

Promethazine for the Treatment of Agitation After Electroconvulsive Therapy

“…18 Peak plasma concentrations occur after 2 to 3 hours when promethazine is administered orally. [18][19][20][21] The elimination half life after oral administration is 12 to 15 hours. 22 Therefore, we decided to administer the medication 2 hours before treatment.…”