PPI meds are toxic with time and dose
2013-06-07 06:02:49 UTC
.2.2 Proton Pump Inhibitors
Proton pump inhibitors are used to treat acid-related dis-
orders such as gastro-oesophageal reflux disease or
oesophagitis/gastritis. Furthermore, PPIs are the treatment
of choice for Helicobacter pylori infection, in combination
with antibiotics. They undergo hepatic metabolism via the
CYP450 pathways and the isoforms CYP2C19 and
CYP3A4 in particular [100]. As a result of the metabolic
pathways of PPIs, CYP2C19 polymorphism has an impact
on their PK behaviour and clinical efficacy. The PK
properties of PPIs (AUC, Cmax and clearance) have been
shown to be significantly different between CYP2C19 PMs
and EMs. The ratios of the mean AUC values in PMs
versus EMs for omeprazole, pantoprazole, lansoprazole
and rabeprazole were 6.3, 6, 4.3 and 1.8, respectively
[101]. These differences in terms of PK properties translate
into differences in their clinical effects. It has been shown
that the mean intragastric pH values were higher in PMs
than in EMs for both omeprazole and lansoprazole [102]. A
meta-analysis, which included 20 studies, showed a sig-
nificant difference in H. pylori eradication rates between
wild-type individuals and carriers of at least one LOF allele
(OR 2.26; 95 % CI 1.58–2.96; P \ 0.0001) when all PPI-
based therapies were combined. The difference was greater
when wild-type homozygous and variant homozygous
patients were compared (OR 2.79; 95 % CI 1.77–4.41;
P \ 0.0001). When individual agents were analysed sep-
arately, a significant difference was observed for omepra-
zole and lansoprazole, whereas no difference between all
genotypes was observed for rabeprazole [103]. This is
probably due to the metabolism of rabeprazole which
involves a non-enzymatic reduction [101].
Proton pump inhibitors are used to treat acid-related dis-
orders such as gastro-oesophageal reflux disease or
oesophagitis/gastritis. Furthermore, PPIs are the treatment
of choice for Helicobacter pylori infection, in combination
with antibiotics. They undergo hepatic metabolism via the
CYP450 pathways and the isoforms CYP2C19 and
CYP3A4 in particular [100]. As a result of the metabolic
pathways of PPIs, CYP2C19 polymorphism has an impact
on their PK behaviour and clinical efficacy. The PK
properties of PPIs (AUC, Cmax and clearance) have been
shown to be significantly different between CYP2C19 PMs
and EMs. The ratios of the mean AUC values in PMs
versus EMs for omeprazole, pantoprazole, lansoprazole
and rabeprazole were 6.3, 6, 4.3 and 1.8, respectively
[101]. These differences in terms of PK properties translate
into differences in their clinical effects. It has been shown
that the mean intragastric pH values were higher in PMs
than in EMs for both omeprazole and lansoprazole [102]. A
meta-analysis, which included 20 studies, showed a sig-
nificant difference in H. pylori eradication rates between
wild-type individuals and carriers of at least one LOF allele
(OR 2.26; 95 % CI 1.58–2.96; P \ 0.0001) when all PPI-
based therapies were combined. The difference was greater
when wild-type homozygous and variant homozygous
patients were compared (OR 2.79; 95 % CI 1.77–4.41;
P \ 0.0001). When individual agents were analysed sep-
arately, a significant difference was observed for omepra-
zole and lansoprazole, whereas no difference between all
genotypes was observed for rabeprazole [103]. This is
probably due to the metabolism of rabeprazole which
involves a non-enzymatic reduction [101].