4.0 OmeprazoleOmeprazole is one of the types of gastric medications which are used commonly to reduce gastric acid secretion. It is used to treat gastrointestinal conditions such as gastroesophageal reflux disease (GERD), excessive acidity in stomach, stomach or peptic ulcer, hypersecretory conditions such as Zollinger-Ellison syndrome and etc. Besides that, this medication is also used to some types of stomach problems which are caused by a type of bacteria known as Helicobacter pylori (H.pylori) together with several types of medications including antibiotics.
Omeprazole is a selective and irreversible proton pump inhibitor in which it works by suppressing stomach acid secretion by specific inhibition of the H+/K+-ATPase found at the secretory surface of gastric parietal cells. Due to the inhibition of this enzyme pumping system, final step of acid production is inhibited.  When administration of omeprazole is stopped, baseline stomach acid secretory activity will eventually return after 3 to 5 days and plateau on the inhibitory effect of omeprazole on acid secretion will occur after 4 days of repeated daily dosing.
Generalization is always a conflicting point when it comes to drug dosing whether should it be applied or not especially among different ethnicities (Asians and Caucasians) in which genetic variation plays an important role in determining metabolizing enzyme constitution or should we apply customized therapy accordingly and this will be discussed more in the pharmacokinetic process part III and IV below. This is a concern as metabolizing enzymes are essential in the pharmacokinetic process of drugs in the body especially metabolism and excretion of drugs which will greatly affect the drug plasma concentration level which will further link to toxicity.4.1 Pharmacokinetics of OmeprazoleI. AbsorptionOmeprazole is acid labile and therefore absorption of omeprazole takes place in the small intestine. This process usually occurs rapidly and can be done on an average of 3 to 6 hours. The bioavailability of this drug is about 40% due to instability in gastric acid as well as a substantial first-pass effect. However, it can be increased slightly by altering the dosage regimen such as by giving repeated dosing.II. DistributionOmeprazole has a volume of distribution of 0.4 L/kg and a high plasma protein binding of almost 95%. In contrast to the long duration of antisecretory action, omeprazole is rapidly eliminated from plasma. The half-life is less than 1 hour, and omeprazole is almost entirely cleared from plasma within 3-4 hours. III. Metabolism Omeprazole undergoes significant hepatic first-pass metabolism and is completely metabolized in the liver by the polymorphic CYP 2C19 enzyme (S-mephenytoin hydroxylase), thus, kinetic differences between racial groups can be observed. Omeprazole is a prodrug and has to be activated prior its action to be exerted and the two major plasma metabolites are the omeprazole sulphone and hydroxy omeprazole. Genetic variation of CYP 2C19 can be explained by a limited number of single-nucleotide polymorphisms, namely, in which includes allele CYP 2C19* 2, CYP 2C19*3, CYP 2C19*4 and CYP 2C19*5. However, it is almost explained for 100% that of for Asian and 85% for white that are poor metabolizers (PM) is due to the mutations of alleles which are the CYP 2C19* 2 and CYP 2C19*3 respectively which is related to inactive enzyme production.  This then brings to a marked ethnic variability in S- mephenytoin hydroxylation, with 2% to 5% PMs in white populations and 13% to 23% PMs in Asian populations in which these two alleles are higher in Chinese compared to Caucasians. Clinical measurements are done and area under the curve (AUC) is used as an indicator as systemic exposure to proton pump inhibitor and it is observed that the concentration is 5-12-times folds in poor metabolizers than in extensive metabolizers (EM).This in turn supports several studies that the AUCs of omeprazole were significantly higher in the Chinese EMs than in the Caucasian EMs possibly due to the higher proportion of heterozygotes in the former than in the latter group.  Therefore, the initial genotyping was done for this enzyme and a much higher dosage must be given to an extensive metabolizer to improve the therapeutic effect of proton pump inhibitors for ideal gastric acid suppression. In another way, poor metabolizers experience superior acid suppression than the rest of the population due to higher blood concentrations of omeprazole which leads to the decrease of dose administered which will then decrease side effects of this drugs. Early identification of ethnic sensitivity is needed for different dosing regimens in a specific ethnic group for substrates of CYP2C19 for omeprazole metabolism in this case for maximum therapeutic effect and minimize drug toxicity and side effects.IV. ExcretionOmeprazole is mainly excreted by the kidneys and the plasma half-life normally between 1/2 to 1 hour and the interesting part about this drug is their effects may persist for days. The elimination half-life observed and obtained in the Chinese PMs and EMs was 2.4 +/- 0.2 and 0.8 +/- 0.2 h–similar to the observations in the Caucasian subjects. However, elimination half-life of the hydroxy metabolite observed to be longer in PMs than in EMs in both of this two populations which was being studied.