Pharmacokinetics of omeprazole given by continuous intravenous infusion to patients with varying degrees of hepatic dysfunction.
OBJECTIVE
To examine the pharmacokinetics of omeprazole during intravenous infusion in patients with varying degrees of liver dysfunction (Child-Pugh categories A to C).


METHODS
Nonblinded single-period study.


METHODS
Thirteen patients, five males and eight females with a mean age of 59 years and proven hepatic cirrhosis, classified according to Child-Pugh criteria as A (n = 5), B (n = 4) or C (n = 4).


METHODS
Each patient received an 80mg bolus of omeprazole over 30 minutes followed by a continuous infusion of 8 mg/h for 47.5 hours. Blood samples were taken frequently throughout the infusion and during the subsequent 24-hour washout period for determination of omeprazole and its metabolites. Laboratory screening was also performed at the start of the study, after 72 hours and at the 14 day follow-up visit.


RESULTS
Data were evaluable for 12 patients. For omeprazole, the mean total area under the plasma concentration-time curve (AUC) was 286.5 micromol x h/L, peak plasma concentration was 14.9 micromol/L and terminal elimination half-life was 4.1 hours; these values were higher than those observed historically in control patient populations. Concentrations of the metabolite omeprazole sulphone were also increased, but there was a decrease in concentrations of hydroxy-omeprazole. Deviations from normal values increased with increasing disease severity for all parameters. For example, in patients with liver dysfunction of Child-Pugh categories A, B and C, AUC(48 )was 240.8, 280.4 and 323.3 micromol x h/L compared with 151.3 micromol x h/L in the historical control population. Despite its altered pharmacokinetics, omeprazole was not associated with any serious or untoward effects.


CONCLUSIONS
Exposure to omeprazole following intravenous administration was higher in patients with liver dysfunction than in the normal population. However, even in patients with severely impaired liver function, the omeprazole plasma concentration did not change by more than 100% and the drug was well tolerated.
Piqué
Josep M
JM
Department of Gastroenterology, Institute of Digestive Diseases, Hospital Clinic, University of Barcelona, Barcelona, Spain. jmpique@clinic.ub.es
Feu
Faust
F
de Prada
Gloria
G
Röhss
Kerstin
K
Hasselgren
Göran
G
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D016001:Confidence Intervals; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008107:Liver Diseases / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D009853:Omeprazole