The pharmacokinetics and pharmacodynamics of hydroxyzine in patients with primary biliary cirrhosis.
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 +/- SD 11.2 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 less than 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Simons
F E
FE
Health Sciences Clinical Research Centre, Faculty of Medicine, University of Manitoba, Canada.
Watson
W T
WT
Chen
X Y
XY
Minuk
G Y
GY
Simons
K J
KJ
D000328:Adult; D000368:Aged; D017332:Cetirizine; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006632:Histamine; D006634:Histamine H1 Antagonists / Q000493:pharmacokinetics; D006801:Humans; D006919:Hydroxyzine / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012882:Skin Tests
D006634:Histamine H1 Antagonists; D006919:Hydroxyzine; D006632:Histamine; D017332:Cetirizine