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(O,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 halflife 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.