PHARMACOKINETICS OF PANTOPRAZOLE IN MAN

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 abs orbed, Its absolute bioavailability is 77% and does not change upon mu ltiple dosing. Following a single oral dose of 40 mg, C-max is approxi mately 2.5 mg/l, with a t(max) of 2 - 3 h. The AUC((0,inf.)) is approx imately 5 mgxh/l. Pantoprazole shows linear pharmacokinetics after bot h i.v, and oral administration. Pantoprazole is extensively metabolize d in the liver, has a total serum clearance of 0.1 l/h/kg, a serum eli mination half-life of about 1.1 h, and an apparent volume of distribut ion of 0.15 l/kg. 98% of pantoprazole is bound to serum proteins. Elim ination half-life, clearance and volume of distribution are independen t of the dose, The main serum metabolite is formed by demethylation at the 4-position of the pyridine ring, followed by conjugation with sul phate. Almost 80% of an oral or intravenous dose is excreted as metabo lites in urine; the remainder is found in feces and originates from bi liary 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. Pantopra zole showed lack of cytochrome P450 interaction with concomitantly adm inistered drugs in any of the studies conducted to date. Lack of inter action was also demonstrated with a coadministered antacid. The absenc e of inductive effects on metabolism after chronic administration was first shown by using antipyrine as a probe for mixed functional oxidat ive cytochrome P450 enzymes, Absence of CYP1A2 induction was confirmed using the specific probe caffeine. As sensitive probes for CYP3A enzy me induction, urinary excretion of D-glucaric acid and 6 beta-hydroxyc ortisol were also unchanged.