Proton pump inhibitors bioavailability

BA, bioavailability CL, total body clearance CrCI, creatinine clearance CYP450, cytochrome P-450 ER, extended-release IR, immediate-release LA, long-acting PPI, proton pump inhibitor Sign., significantly SR, sustained-release TD, transdermal. 

Proton pump inhibitors cause a profound and long-lasting inhibition of gastric acid secretion therefore, proton pump inhibitors may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (eg, ketoconazole, ampicillin, iron salts, digoxin, cyanocobalamin). 

Other proton pump inhibitors e.g., lansoprazole is more potent than omeprazole and has higher bioavailability, rapid onset of action and longer duration of action. Pantoprazole is the new H+K+ATPase inhibitor with similar properties and action to omeprazole. 

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. 

The pharmacokinetics of available proton pump inhibitors are shown in Table 63-2. Their bioavailability is decreased approximately 50% by food hence, the drugs should be administered on an empty stomach. In a fasting state, only 10% of proton pumps are actively secreting acid and susceptible to inhibition. Proton pump inhibitors should be administered approximately 1 hour before a meal (usually breakfast or dinner), so that the peak serum concentration coincides with the maximal activity of proton pump secretion. The drugs have a short serum half-life of about 1.5 hours however, the duration of acid inhibition lasts up to 24 hours due to the irreversible inactivation of the proton pump. At least 18 hours are required for synthesis of new H+/K+ ATPase pump molecules. Because not all proton pumps are inactivated with the first dose of medication, up to 3-4 days of daily medication are required before the full acid-inhibiting potential is reached. Similarly, after stopping the drug, it takes 3-4 days for full acid secretion to return. 

DIPYRIDAMOLE PROTON PUMP INHIBITORS Possible 1 bioavailability of dipyridamole Dipyridamole tablets require an acidic environment for adequate dissolution an t in pH of the stomach impairs dissolution and therefore may 1 absorption of the drug t the dose of dipyridamole or consider using an alternative antiplatelet drug... 

NIFEDIPINE PROTON PUMP INHIBITORS - OMEPRAZOLE Possible t efficacy and adverse effects Small t in bioavailability possible via t intragastric pH Unlikely to be clinically significant... 

DIGOXIN PROTON PUMP INHIBITORS Plasma concentrations of digoxin are possibly t by proton pump inhibitors Small t in bioavailability possible via t intragastric pH or altered intestinal P-gp transport Not thought to be clinically significant unless a poor CYP2C19 metabolizer. No specific recommendations. Different proton pump inhibitors may interaction differently - monitor if changing therapy or doses... 

Esomeprazole 26 Gastric proton pump (inhibitor) Analog of omeprazole (S)-Enantiomer of omeprazole, which is racemic Enhanced oral bioavailability Esophagitis GI tract... 

Loss of gastric acidity from chronic proton pump inhibitor treatment may affect the bioavailability of such drugs as ketoconazole, ampicillin esters, and iron salts. Chronic therapy, with proton pump inhibitors has been linked to increased frequency of hip fractures, possibly secondary to decreased absorption of calcium. 

The bioavailability of ketoconazole is reduced by both omeprazole and rabeprazole. Other proton pump inhibitors are expected to behave similarly. Omeprazole also markedly reduces the absorption of itraconazole capsules, but not the oral solution. Proton pump inhibitors are predicted to reduce the bioavailability of posaconazole. The bioavailabilities of fluconazole and voriconazole are not significantly affected by omeprazole. Esomeprazole levels may also be Increased by voriconazole.Omeprazole levels are Increased by ketoconazole, and markedly increased by fluconazole and voriconazole. 

There seem to be no reports about ketoconazole and other proton pump inhibitors but they are also expected to interact to reduce the bioavailability of the ketoconazole, but the extent is not known. 

Omeprazole markedly increases the absorption and bioavailability of bismuth from tripotassium dicitratobismuthate and bismuth biskalcitrate. Other proton pump inhibitors are expected to interact similarly. However, this is probably unlikely to be clinically relevant. 

The bioavailability of enteric-coated preparations of aspirin, diclofenac, and ketoprofen are unaffected by omeprazole, see NSAIDs or Aspirin + Proton pump inhibitors , p.l55. 

An active substance, although initially released from its dosage form (and dissolved), may become unavailable for absorption due to reactimis with other medicines or food components [4]. An example is the formation of insoluble complexes of tetracycline with calcium or aluminium ions from antacids or milk products. Interaction (chelation or binding) with iron ions leads to a reduced absorption for a variety of active substances such as doxycycline, penicillamine, methyldopa and ciprofloxacin. The absorption of active substances showing pH-dependent dissolution behaviour may be influenced by medicines that influence the gastric pH, such as H2-antagonists, proton pump inhibitors and antacids. Antimycotic active substances such as ketoconazole or itraconazole dissolve better in acidic fluids. Therefore their bioavailability may be increased by the concomitant use of an acidic drink like cola, whereas the concomitant use of antacids or proton pump inhibitors is likely to reduce the bioavailability. Concomitant use of milk may increase the dissolution of acidic active substances, whereas fats from food may increase the bioavailability of lipophilic active substances like albendazole and griseofulvin. 

Like other clinically available azole antifiingal agents, co-administration with H2-antagonists or proton pump inhibitors reduces bioavailability as a consequence of a reduction in gastric acidity. 

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