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.