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Abstract:  The purpose of this open-label, nonrandomized, crossover trial was to determine the bioavailability of promethazine formulated in a topical Pluronic lecithin organogel. The study was performed at a tertiary care facility. The study subjects were 15 healthy adult white men aged 21 to 40 years, all of whom met the inclusion criteria. Volunteers with a medical history of promethazine hypersensitivity, epileptic disorder, or extrapyramidal reactions, or who had an abnormal skin condition or were taking any medications were excluded. Promethazine 50 mg in a Pluronic lecithin organogel was applied once to the skin of the nondominant wrist of each of 15 subjects, and the application site was covered with an adhesive bandage. Blood samples were collected at baseline (time zero) before drug administration and at 15, 30, 60, 120, 240, and 360 minutes after drug administration. After a 21-day washout period, 10 of the subjects returned for administration of a single dose of intravenous promethazine 25 mg, and blood samples were again collected at the same time intervals as after the topical dose. A high-performance liquid chromatographic method was used to determine serum concentrations of promethazine. The calculated absolute bioavailability of topical promethazine was 2%. Mean AUC0-8 were 16.63 ng•mL/hour for the topical preparation and 407.15 ng•mL/hour for the intravenous dose. At least 50% of the subjects who received the topical promethazine preparation experienced sedation and 73% experienced drowsiness; however, 100% of those who received intravenous promethazine experienced sedation. Although serum concentrations after application of topical promethazine were much lower than after parenteral administration, the study demonstrated that the topical promethazine formulation was absorbed systemically. These data suggest that further research regarding the bioavailability of promethazine in a topically applied Pluronic lecithin organogel is warranted. Clinical trials are needed that focus on the antiemetic efficacy of this formulation in similar and other populations.

Related Keywords: James K. Glisson, MD, PharmD, Rebecca L. Wood, PharmD, Patrick B. Kyle, John D. Cleary, PharmD, FCCP, promethazine, antiemetic, transdermal preparation, percutaneous drug delivery, emesis, nausea, vomiting, phenothiazine, Pluronic lecithin organogel, PLO, drug carrier, drug vehicle, bioavailability, topical preparation

Related Categories: GASTROENTEROLOGY, PEER-REVIEWED, DOSAGE FORMS/DRUG CARRIERS

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