Pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories and oral syrup to healthy subjects

Am J Health Syst Pharm. 2000 Aug 15;57(16):1499-505. doi: 10.1093/ajhp/57.16.1499.

Abstract

The pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories at three dosage strengths and oral syrup were studied. The study had an open-label, randomized, crossover design. At intervals of five to nine days, healthy volunteers were given two 12.5-mg promethazine rectal suppositories, one 25-mg suppository, one 50-mg suppository, or 50 mg (10 mL) of promethazine oral syrup. Blood samples were collected before each dose and at intervals from 0.5 to 48 hours afterward. Promethazine concentration was determined by high-performance liquid chromatography, and pharmacokinetic values were calculated with noncompartmental methods. Thirty-six subjects (18 men and 18 women) completed the study. Absorption was highly variable for all the formulations. On average, absorption was more rapid and the maximum plasma concentration (Cmax) higher for the syrup than for the suppositories. Cmax was significantly lower for the 50-mg suppository (mean, 9.04 ng/mL) than for the syrup (19.3 ng/mL). The time to Cmax (tmax) was significantly shorter for the syrup (mean, 4.4 hours) than for the suppositories (6.7-8.6 hours). There were no significant differences in dose-normalized Cmax among the three suppository treatments. Area under the concentration-versus-time curve (AUC) was comparable between the syrup and the 50-mg suppository and between the treatments with two 12.5-mg suppositories and the 25-mg suppository. Elimination profiles were similar among all treatments (mean half-life [t1/2], 16-19 hours). There were no significant differences in pharmacokinetics on the basis of sex or race. The mean relative bioavailability for the three suppository treatments ranged from 70% to 97%. Individual relative bioavailabilities ranged from 4% to 343%. The pharmacokinetics of promethazine administered in oral syrup and rectal suppositories were highly variable, but, in general, the suppositories produced a lower Cmax and later tmax than the syrup. All formulations were comparable in terms of dose-normalized AUC and t1/2, and the three suppository treatments were comparable in terms of dose-normalized Cmax.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Administration, Rectal
  • Adult
  • Analysis of Variance
  • Area Under Curve
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Female
  • Half-Life
  • Histamine H1 Antagonists / administration & dosage
  • Histamine H1 Antagonists / pharmacokinetics*
  • Humans
  • Male
  • Promethazine / administration & dosage
  • Promethazine / pharmacokinetics*
  • Suppositories

Substances

  • Histamine H1 Antagonists
  • Suppositories
  • Promethazine