Pharmacokinetics of pantoprazole in man

Int J Clin Pharmacol Ther. 1996 May;34(1 Suppl):S7-16.

Abstract

The proton pump inhibitor pantoprazole is a substituted benzimidazole sulphoxide for the treatment of acid-related gastrointestinal diseases such as reflux esophagitis, duodenal and gastric ulcers. Pantoprazole, administered as a 40 mg enteric coated tablet, is quantitatively absorbed. Its absolute bioavailability is 77% and does not change upon multiple dosing. Following a single oral dose of 40 mg, Cmax is approximately 2.5 mg/l, with a tmax of 2-3 h. The AUC(0,inf.) is approximately 5 mgxh/l. Pantoprazole shows linear pharmacokinetics after both i.v. and oral administration. Pantoprazole is extensively metabolized in the liver, has a total serum clearance of 0.1 l/h/kg, a serum elimination half-life of about 1.1 h, and an apparent volume of distribution of 0.15 l/kg. 98% of pantoprazole is bound to serum proteins. Elimination half-life, clearance and volume of distribution are independent of the dose. The main serum metabolite is formed by demethylation at the 4-position of the pyridine ring, followed by conjugation with sulphate. Almost 80% of an oral or intravenous dose is excreted as metabolites in urine; the remainder is found in feces and originates from biliary secretion. The pharmacokinetics of pantoprazole are unaltered in patients with renal failure. In patients with severe liver cirrhosis, the decreased rate of metabolism results in a half-life of 7-9 h. The clearance of pantoprazole is only slightly affected by age, its half-life being approximately 1.25 h in the elderly. Concomitant intake of food had no influence on the bioavailability of pantoprazole. Pantoprazole showed lack of cytochrome P450 interaction with concomitantly administered drugs in any of the studies conducted to date. Lack of interaction was also demonstrated with a coadministered antacid. The absence of inductive effects on metabolism after chronic administration was first shown by using antipyrine as a probe for mixed functional oxidative cytochrome P450 enzymes. Absence of CYP1A2 induction was confirmed using the specific probe caffeine. As sensitive probes for CYP3A enzyme induction, urinary excretion of D-glucaric acid and 6 beta-hydroxycortisol were also unchanged.

Publication types

  • Review

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Adolescent
  • Adult
  • Aged
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / pharmacokinetics*
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacokinetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Omeprazole / analogs & derivatives
  • Pantoprazole
  • Proton Pump Inhibitors*
  • Sulfoxides / administration & dosage
  • Sulfoxides / pharmacokinetics*

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Benzimidazoles
  • Enzyme Inhibitors
  • Proton Pump Inhibitors
  • Sulfoxides
  • Pantoprazole
  • Omeprazole