The Pharmacokinetics and Pharmacodynamics of Hydroxyzine in Patients with Primary Biliary Cirrhosis

Abstract

Hydroxyzine, a potent H₁-receptor antagonist often used for relief of pruritus in patients with hepatic dysfunction, was studied in eight patients, mean age 53.4 ± SD11.2 years, with primary biliary cirrhosis. The patients ingested a single dose of hydroxyzine, 0.7 mg/kg (mean dose 43.9 ± 6.6 mg). Before the dose, then hourly for 6 hours, every 2 hours from 6–12 hours, at 24 hours, and every 24 hours for 6 days, serum hydroxyzine and cetirizine were measured and an intradermal injection of 0.01 mL of a 0.1 mg/mL solution of histamine phosphate was performed. Wheals and flares were traced at 10 minutes and the areas were calculated. Mean peak hydroxyzine levels of 116.5 ± 60.6 ng/mL occurred at 2.3 ± 0.7 hours and mean peak cetirizine levels of 500.4 ± 302.0 ng/mL occurred at 4.8 ± 2.8 hours. The mean serum elimination half-life of hydroxyzine was 36.6 ± 13.1 hours, and the mean serum elimination half-life of cetirizine was 25.0 ± 8.2 hours. The mean hydroxyzine clearance rate was 8.65 ± 7.46 mL/min/kg, and the mean volume of distribution was 22.7 ± 13.3 L/kg. The mean wheal area was suppressed (P < 0.01) from 1 to 120 hours, with maximal suppression from 2 to 48 hours. The mean flare area was suppressed from 1 to 144 hours, with maximal suppression from 3 to 24 hours (P < 0.01). All patients became sleepy from 0.5 to 6 hours. Blurred vision, dizziness and dry mouth each occurred in two patients. Hydroxyzine elimination is impaired in patients with primary biliary cirrhosis. If hydroxyzine is prescribed for pruritus relief in these patients, the dosage regimen may need to be modified.