Omeprazole absorption

Howden CW, Reid JL (1988) The effect of antacids and metoclopramide on omeprazole absorption and disposition. Brit J Clin Pharmacol 25 779-781... 

Vitamin B12 generally is well tolerated and exhibits minimal adverse effects. Injection-site pain, pruritus, rash, and diarrhea have been reported. Drug interactions have been observed with omeprazole and ascorbic acid that decrease oral absorption. 

The consequence of bacterial bile acid metabolism [66, 74,77] is hardly clinically significant malabsorption [6] in otherwise healthy individuals [32,79], but in predisposed individuals this may be different. Accordingly, omeprazole interferes with the absorption of vitamin B12 [80-83] and protein assimilation [84], The mechanism for altered vitamin B12 absorption is prevention of its cleavage from dietary protein [83], for which the importance of the concurrent bacterial overgrowth has not yet been ruled out. 

Saltzman JR, Kemp JA, Golner BB, Pedrosa MC, Dallal GE, Russell RM Effect of hypo-chlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption. J Am CollNutr 1994 13 584-591. 

Phenytoin (Dilantin) [Anticenvulsant/Hydantoin] Uses Sz disorders Action X Sz spread in the motor cortex Dose Load Adults Peds. 15-20 mg/kg IV, 25 mg/min max or PO in 400-mg doses at 4-h intervals Maint Adults. Initial, 200 mg PO or IV bid or 300 mg hs then follow levels Peds. 4-7 mg/kg/24h PO or IV -s- daily-bid avoid PO susp (erratic absorption) Caution [D, +] Contra Heart block, sinus bradycardia Disp Caps, susp, inj SE Nystag-mus/ataxia early signs of tox gum hyperplasia w/ long-term use. IV BP, bradycardia, arrhythmias, phlebitis peripheral neuropathy, rash, blood dyscrasias, Stevens-Johnson synd Notes Levels Trough Just before next dose Therapeutic Peak 10-20 mcg/mL Toxic >20 mcg/mL phenytoin albumin bound, levels = bound free phenytoin w/ i albumin azotemia, low levels may be therapeutic (nl free levels) Interactions T Effects W/ amiodarone, allopurinol, chloramphenicol, disulfiram, INH, omeprazole, sulfonamides, quinolones, trimethoprim t... 

These agents are second generation proton pump inhibitors. Their mode of action is similar to omeprazole. Structural differences give more rapid absorption and greater bioavailability of lansoprazole. Lansoprazole has less effect on P-450 enzymes, while interaction with pantoprazole is insignificant. Lansoprazole has a significant antibacterial effect on Helicobacter pylori. 

Proton pump inhibitors (PPIs), eg, omeprazole, lansoprazole Irreversible blockade of H +, K+-ATPase pump in active parietal cells of stomach Long-lasting reduction of stimulated and nocturnal acid secretion Peptic ulcer, gastroesophageal reflux disease, erosive gastritis Half-lives much shorter than duration of action low toxicity reduction of stomach acid may reduce absorption of some drugs and increase that of others... 

The infrared (IR) absorption spectrum of omeprazole was obtained in a KBr pellet using a Perkin-Elmer IR spectrophotometer. The IR spectrum is shown in Fig. 4.8, where the principal peaks were observed and the assignments for the major IR absorption bands are listed in Table 4.6. 

TABLE 4.6 Vibrational assignments for omeprazole infrared absorption bands... 

Test B Examine by IR absorption spectrophotometry, according to the general method (2.2.24), comparing with the spectrum obtained with omeprazole CRS. If the spectra obtained in the solid state show differences, dissolve the substance to be examined and the reference substance separately in methanol R, evaporate to dryness and record new spectra using the residues. 

Test B Infrared absorption—Carry out this test as directed in the general procedure (197 K). The IR absorption spectrum of a potassium bromide dispersion of omeprazole previously dried, exhibits maxima only at the same wavelength as that of similar preparation of USP Omeprazole RS. 

El-Kousy and Bebawy [31] described two stability-indicating spectro-photometric methods for the determination of omeprazole in the presence of its photodegradation products. In the first method, omeprazole from capsules or vials were dissolved in acetonitrile/water (1 1) and UV-VIS spectrophotometry used to determine the first-, second-, and third-derivative absorption curves between 200 and 400 nm. The level of omeprazole was assayed from the values of ordinates of the three curves at 290.4,... 

Mixing methanolic samples with 2 ml methanolic 0.5% p-dimetyyla-mino benzaldehyde and 2 ml sulfuric acid with cooling and agitation, dilution to 10 ml with methanol and absorbance measurement at 420 nm within 20 min. Beer s law was obeyed from 0.5-5, 4-20, and 12.5-125 ng/ml of omeprazole, for the three methods, respectively, and the corresponding molar absorptivities (e) were 42,800,6400, and 2380. The relative standard derivations (n = 6) were 0.29-0.41% and recoveries were 98.17-100.1%. 

Pharmacokinetics Omeprazole and lansoprazole are enteric-coated to protect them from premature activation by gastric acid. After absorption in the duodenum, they are transported to the acid parietal cell canaliculus, where they are converted to active species. Metabolites of these agents are excreted in urine and feces. 

Impaired absorption of oral form with chloramphenicol, neomycin, H2 antagonists, omeprazole, and colchicine... 

GUMEPIRIDE H2 RECEPTOR BLOCKERS-CIMETIDINE, RANITIDINE t plasma concentrations of glimepiride and t risk of hypoglycaemic episodes Cimetidine and ranitidine i renal elimination of glimepiride and t intestinal absorption of glimepiride. Cimetidine is also an inhibitor of CYP2D6 and CYP3A4 Consider alternative acid suppression, e.g. proton pump inhibitor (not omeprazole), and monitor more closely... 

TRIPOTASSIUM DICITRATOBISMUTHATE PROTON PUMP INHIBITORS - OMEPRAZOLE t adverse effects of tripotassium dicitratobismuthate T absorption Do not use together for more than 16 weeks. Bismuth salicylate and subnitrate do not interact... 

Figure 4.7. Scheme of the relation between acidic instability, intestinal absorption, and acid transformation of omeprazole-like H lK -ATPase inhibitors. 

Omeprazole is rapidly and completely metabolized after intestinal absorption. Oxidative processes for metabolism are predominant and three main metabolites of omeprazole have been identified the corresponding sulphone and sulphide as well as hydroxyomeprazole. Omeprazole sulphone is further metabolized or it is eliminated in the faeces. Renal excretion is the predominant route of elimination of omeprazole metabolites [20, 28, 110]. The metabolism of lansoprazole in humans is comparable to that of omeprazole it is converted to hydroxylansoprazole, lansoprazole-sulphone, lansoprazole-sulphide and the hydroxylated sulphone [111]. 

Gastrointestinal drugs. Avoid cimetidine and omeprazole which inhibit the clearance of R warfarin, and sucralfate which may impair its absorption. Ranitidine may be used but INR should be checked if the dose is high. Most antacids are safe. 

Omeprazole is a proton pump inhibitor. Headache, skin rash, and diarrhea have all been recorded by adverse event registries sufficiently often to suggest causal relations (1). Omeprazole is a modest inhibitor of CYP isoforms. Interactions are less likely than with cimetidine and are probably of no practical importance. However, omeprazole reduces the absorption of drugs that require a low gastric pH (ketoconazole, iron salts, ampicilhn) and can inhibit the hepatic clearance of some drugs (diazepam, warfarin, phenytoin) (2). 

The effects of omeprazole 40 mg/day on the pharmacokinetics of itraconazole 200 mg have been studied in 11 healthy volunteers (37). Omeprazole reduced the absorption of itraconazole. As the absorption of itraconazole is pH-dependent (it requires a pH of under 3.0 for complete dissolution and absorption) the likely explanation for this interaction is the effect of omeprazole on gastric pH. 

---