Proton pump inhibitors: actions and reactions

Mullin, James M.; Gabello, Melissa; Murray, Lisa; Farrell, C.; Bellows, Jillan; Wolov, Kevin; Kearney, Keith R.; Rudolph, David; Thornton, J. Douglas

doi:10.1016/j.drudis.2009.03.014

Cited by 95 publications

(76 citation statements)

References 152 publications

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“…These results imply that the short‐term use of esomeprazole poses a low risk of plasma accumulation in dogs. According to a previous study, 3–5 days of administration are required to reach the maximum efficacy of omeprazole for reducing gastric acid 2. Thus, the differences in efficacy between single and repeated PO doses are thought to be associated with the saturation of gastric proton pumps rather than with PK differences after repeated PO administration.…”

Section: Discussionmentioning

confidence: 99%

“…Omeprazole is widely used as a proton pump inhibitor (PPI) for treating and preventing acid‐related diseases in human and veterinary medicine, and it is administered as a racemic mixture of 2 optical isomers: S‐omeprazole (esomeprazole) and R‐omeprazole 1, 2. These 2 enantiomers are converted in the same proportions to an achiral active form in the acidic compartment of gastric parietal cells 3…”

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confidence: 99%

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Pharmacokinetics and Acid Suppressant Efficacy of Esomeprazole after Intravenous, Oral, and Subcutaneous Administration to Healthy Beagle Dogs

Hwang

Jeong

Song

et al. 2017

Veterinary Internal Medicne

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BackgroundEsomeprazole is an S‐enantiomer of omeprazole that has favorable pharmacokinetics and efficacious acid suppressant properties in humans. However, the pharmacokinetics and effects on intragastric pH of esomeprazole in dogs have not been reported.ObjectiveTo determine the pharmacokinetics of esomeprazole administered via various routes (PK study) and to investigate the effect of esomeprazole on intragastric pH with a Bravo pH monitoring system (PD study).AnimalsSeven adult male Beagle dogs and 5 adult male Beagle dogs were used for PK and PD study, respectively.MethodsBoth studies used an open, randomized, and crossover design. In the PK study, 7 dogs received intravenous (IV), subcutaneous (SC), and oral doses (PO) of esomeprazole (1 mg/kg). Each treatment period was separated by a washout period of at least 10 days. Esomeprazole plasma concentrations were measured by HPLC/MS/MS. In the efficacy study, intragastric pH was recorded without medication (baseline pH) and following IV, SC, and PO esomeprazole dosing regimens (1 mg/kg) in 5 dogs.ResultsThe bioavailability of esomeprazole administered as PO enteric‐coated granules and as SC injections was 71.4 and 106%, respectively. The half‐life was approximately 1 hour. Mean ± SD percent time intragastric pH was ≥3 and ≥4 was 58.9 ± 21.1% and 40.9 ± 17.3% for IV group, 75.8 ± 16.4% and 62.7 ± 17.7% for SC group, 88.2 ± 8.9% and 82.5 ± 7.7% for PO group, and 12.5 ± 3.6% and 3.7 ± 1.8% for baseline. The mean percent time with intragastric pH was ≥3 or ≥4 was significantly increased regardless of the dosing route (P < .05).ConclusionThe PK parameters for PO and SC esomeprazole administration were favorable, and esomeprazole significantly increased intragastric pH after IV, PO, and SC administration. IV and SC administration of esomeprazole might be useful when PO administration is not possible. No significant adverse effects were observed.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Pharmacokinetics and Acid Suppressant Efficacy of Esomeprazole after Intravenous, Oral, and Subcutaneous Administration to Healthy Beagle Dogs

Hwang

Jeong

Song

et al. 2017

Veterinary Internal Medicne

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“…The consistent administration of PPIs for at least one year may lead to low levels of circulating divalent cations, including magnesium and copper [23,24] . Although malabsorption has been suspected, PPI-induced iron, zinc and B12 deficiencies have not been shown to be clinically significant [10,13,15,[25][26][27] .…”

Section: General Tolerance Of Ppismentioning

confidence: 99%

Proton pump inhibitor-associated pneumonia: Not a breath of fresh air after all?

Fohl

Regal²

2011

WJGPT

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Over the past two decades, proton pump inhibitors (PPIs) have emerged as highly effective and relatively safe agents for the treatment of a variety of gastrointestinal disorders. Unfortunately, this desirable pharmacological profile has also contributed to superfluous and widespread use in both the inpatient and outpatient settings. While generally well-tolerated, research published over the last decade has associated these agents

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“…These bind irreversibly to hydrogen potassium ATPase pumps and may elevate gastric luminal pH to as high as pH 7. 125 The duration of PPI-induced gastric acid suppression [125][126][127][128] may potentially be sustained for several days after therapy cessation. 129 Coadministration of an acid-reducing agent may markedly impair systemic absorption of many of the molecularly targeted agents (which exhibit pHdependent solubility), 128 potentially causing suboptimal tumor exposure and development of drug resistance pathways.…”

Section: Comedication Usementioning

confidence: 99%

Pharmacokinetic‐Guided Dosing of New Oral Cancer Agents

Lucas

Martin

2017

The Journal of Clinical Pharma

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Generally, licensed drug-dosing recommendations for chemotherapy are based on results from clinical trials in which subjects are usually of relatively normal body size, middle-aged, and are relatively racially homogeneous, with minimal comorbidity and specific tumor characteristics. Very few nontrial patients meet these characteristics, resulting in clinical practice having to extrapolate dosing recommendations to the specific patient. There is insufficient research on the impact of obesity-associated physiological changes prevalent in patients with common cancers on standard pharmacokinetic and pharmacodynamic parameters. Yet quantifying the influence of obesity on the pharmacology of chemotherapy is vital, as dosing inappropriate for body composition (ie, flat dosing or mg/kg based on total body weight) may increase the risk of adverse events and reduce clinical effectiveness. Unfortunately, there are few cancer guidelines to aid clinicians in selecting the optimal dose in the obese-even recent guidelines are based predominantly on clinical opinion/current practice in treating obese patients, rather than evidence. Data in many other vulnerable groups, for example, those with significant comorbidity and older patients, are also scarce. Because of the known limitations of body surface area-guided dosing, therapeutic drug monitoring or pharmacokinetic-guided dosing, which predicts an individual's exposure, has increasingly been shown to be a powerful tool in cancer therapy. Used appropriately, it can adjust for differences in pharmacokinetic parameters not considered when body size-based dosing or "one dose fits all" is used. This review will focus predominantly on the rationale for pharmacokinetic-guided dosing of the newer oral molecularly targeted antineoplastics in people whose drug exposure is not predicted by their physiology or body composition.

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Proton pump inhibitors: actions and reactions

Cited by 95 publications

References 152 publications

Pharmacokinetics and Acid Suppressant Efficacy of Esomeprazole after Intravenous, Oral, and Subcutaneous Administration to Healthy Beagle Dogs

Pharmacokinetics and Acid Suppressant Efficacy of Esomeprazole after Intravenous, Oral, and Subcutaneous Administration to Healthy Beagle Dogs

Proton pump inhibitor-associated pneumonia: Not a breath of fresh air after all?

Pharmacokinetic‐Guided Dosing of New Oral Cancer Agents

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