-
Postgraduate Medical Journal Jan 2022
Topics: Carcinoma, Hepatocellular; Hepatitis; Humans; Liver Neoplasms; Pantoprazole
PubMed: 33273111
DOI: 10.1136/postgradmedj-2020-138838 -
American Journal of Therapeutics 2018
Topics: Aged; Gastroesophageal Reflux; Humans; Male; Pancreas; Pancreatitis, Chronic; Pantoprazole; Proton Pump Inhibitors; Tomography, X-Ray Computed
PubMed: 28282309
DOI: 10.1097/MJT.0000000000000567 -
Praxis 2019
Topics: Gastroesophageal Reflux; Humans; Pantoprazole; Proton Pump Inhibitors
PubMed: 31822229
DOI: 10.1024/1661-8157/a003342 -
Frontiers in Veterinary Science 2022Development of abomasal ulceration is a large concern, especially within calves; however, there is a paucity of research into the use of gastro protectants in ruminant...
INTRODUCTION
Development of abomasal ulceration is a large concern, especially within calves; however, there is a paucity of research into the use of gastro protectants in ruminant species. Proton pump inhibitors, such as pantoprazole, are widely used in humans and companion animals. Their efficacy in ruminant species is undetermined. The objectives of this study were to 1) estimate the plasma pharmacokinetic parameters for pantoprazole in neonatal calves after three days of intravenous (IV) or subcutaneous (SC) administration, and 2) measure the effect pantoprazole had on abomasal pH over the treatment period.
METHODS
Pantoprazole was administered to 6 Holstein-Angus cross bull calves at a dose of 1 mg/kg (IV) or 2 mg/kg (SC), once a day (every 24 h) for three days. Plasma samples were collected over a 72 h period and analyzed HPLC-UV for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Abomasal (n= 8) samples were collected abomasal cannulas over a 12 h period, per calf per day. Abomasal pH was determined a bench top pH analyzer.
RESULTS
Following Day 1 of IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 199.9 mL/kg/h, 1.44 h, and 0.51 L/kg, respectively. On Day 3 of IV administration, the reported values were 192.9 mL/kg/h, 2.52 h, and 1.80 L/kg mL, respectively. Elimination half-life and volume of distribution (V/F) of pantoprazole following SC administration were estimated at 1.81 h and 0.55 L/kg, respectively, on Day 1; and 2.99 h and 2.82 L/kg, respectively, on Day 3.
DISCUSSION
The reported values for IV administration were similar to those previously reported in calves. SC administration appears to be well absorbed and tolerated. The sulfone metabolite was detectable for 36 h after the last administration for both routes. Abomasal pH was significantly higher than the pre-pantoprazole pH 4, 6, and 8 h after administration in both the IV and SC groups. Further studies of pantoprazole as a treatment/preventative for abomasal ulcers are warranted.
PubMed: 36794231
DOI: 10.3389/fvets.2022.1101461 -
Archives of Pharmacal Research Jan 2024Pantoprazole is used to treat gastroesophageal reflux disease (GERD), maintain healing of erosive esophagitis (EE), and control symptoms related to Zollinger-Ellison...
Pantoprazole is used to treat gastroesophageal reflux disease (GERD), maintain healing of erosive esophagitis (EE), and control symptoms related to Zollinger-Ellison syndrome (ZES). Pantoprazole is mainly metabolized by cytochrome P450 (CYP) 2C19, converting to 4'-demethyl pantoprazole. CYP2C19 is a genetically polymorphic enzyme, and the genetic polymorphism affects the pharmacokinetics and/or pharmacodynamics of pantoprazole. In this study, we aimed to establish the physiologically based pharmacokinetic (PBPK) model to predict the pharmacokinetics of pantoprazole in populations with various CYP2C19 metabolic activities. A comprehensive investigation of previous reports and drug databases was conducted to collect the clinical pharmacogenomic data, physicochemical data, and disposition properties of pantoprazole, and the collected data were used for model establishment. The model was evaluated by comparing the predicted plasma concentration-time profiles and/or pharmacokinetic parameters (AUC and C) with the clinical observation results. The predicted plasma concentration-time profiles in different CYP2C19 phenotypes properly captured the observed profiles. All fold error values for AUC and C were included in the two-fold range. Consequently, the minimal PBPK model for pantoprazole related to CYP2C19 genetic polymorphism was properly established and it can predict the pharmacokinetics of pantoprazole in different CYP2C19 phenotypes. The present model can broaden the insight into the individualized pharmacotherapy for pantoprazole.
Topics: Cytochrome P-450 CYP2C19; Genotype; Pantoprazole; Phenotype; Polymorphism, Genetic; Humans
PubMed: 38150171
DOI: 10.1007/s12272-023-01478-7 -
European Journal of Clinical... Jan 2022Long-term use of proton pump inhibitors (PPIs) has been linked to an increased risk of osteoporosis, with various indirect mechanisms so far identified. Although no... (Observational Study)
Observational Study
BACKGROUND
Long-term use of proton pump inhibitors (PPIs) has been linked to an increased risk of osteoporosis, with various indirect mechanisms so far identified. Although no direct underlying mechanism for effect on bone cells have been investigated with the use of PPIs. Melastatin-like transient receptor potential 7 (TRPM7)channel has been engaged in the proliferation of bone cells. TRPM7 channel is regulated by extracellular Mg and Ca level, that further encourages to analyse if any imbalance with pantoprazole usage could alter bone remodelling process mediated by TRPM7.
OBJECTIVES
The present study was conducted to investigate the effect of pantoprazole on the calcium and magnesium level, the cations involved in the bone remodelling process, as well as role of the TRPM7 channel in the proliferation of bone cells.
METHODS
A cytotoxicity study was carried out to study the effect of pantoprazole on the bone cell using MC3T3-E1 cell line, together with the expression of TRPM7 was determined post-pantoprazole treatment. An in vivo study in rats was carried out for estimation of Ca, Mg and Ca/Mg ratio as well as bone strength was measured over a duration of 4 weeks and 8 weeks with the treatment of pantoprazole. A pilot-scale clinical study was carried out in patients with a fracture to support the evidence of preliminary findings from in-vitro and in vivo studies.
RESULTS
MC3T3-E1 cell line treated with pantoprazole showed decreased cell viability in a dose-dependent manner and reduced expression of TRPM7 channel, evidencing interaction of TRPM7 and pantoprazole in the bone remodelling process. A pilot study conducted on 12 patients having major fractures showed changes in serum Mg and Ca levels over a period of 1 month as well as the animal study also showed ionic imbalance over 8-week treatment with pantoprazole. Bone density measured for the patient at the end of the 1-month treatment was found to be in the osteopenic category, together with the animal study which showed a decrease in femur bone strength for the animal treated with pantoprazole over a period of 8 weeks.
CONCLUSION
The study findings proved a negative impact of pantoprazole use on Ca and Mg levels, which can impact TRPM7-mediated bone remodelling which serves to be a possible mechanism for osteoporosis upon pantoprazole use.
Topics: Animals; Bone Density; Bone and Bones; Calcium; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Female; Humans; Magnesium; Male; Pantoprazole; Pilot Projects; Prospective Studies; Proton Pump Inhibitors; Rats; Rats, Wistar; TRPM Cation Channels
PubMed: 34714373
DOI: 10.1007/s00228-021-03237-3 -
African Journal of Paediatric Surgery :... 2022Previous studies demonstrated faster correction of metabolic derangement associated with hypertrophic pyloric stenosis with pre-operative intravenous (IV) histamine-2...
CONTEXT
Previous studies demonstrated faster correction of metabolic derangement associated with hypertrophic pyloric stenosis with pre-operative intravenous (IV) histamine-2 receptor antagonists.
AIMS
We investigated if similar outcomes are achieved with IV pantoprazole, a proton-pump inhibitor (PPI), including the subgroup of delayed presenters in the South African setting.
SETTINGS AND DESIGN
A 5-year retrospective record review (January 2014-December 2018) compared the rate of metabolic correction in patients with hypertrophic pyloric stenosis at two tertiary centres.
SUBJECTS AND METHODS
One centre routinely administers IV pantoprazole (1 mg/kg daily) preoperatively (PPI group) and the other does not (non-PPI group). Fluid administration, chloride supplementation and post-operative emesis were evaluated.
STATISTICAL ANALYSIS
Spearman's rank correlation coefficient was used to calculate statistical significance for discrete dependent variables. Continuous variables were compared between the groups using the Student t-test. Fisher's exact contingency tables were used to classify categorical data and to assess the significance of outcome between two treatment options. P < 0.05 was considered statistically significant.
RESULTS
Forty-two patients received IV pantoprazole and 24 did not. The mean time of metabolic correction was 8 h shorter in the PPI group (P = 0.067). Total pre-operative chloride administration correlated to the rate of metabolic correction in both cohorts (P < 0.0001). Profound hypochloraemia (chloride <85 mmol/l) was corrected 23 h faster in the PPI group (P < 0.004). Post-operative emesis was noted: 0.45 episodes/patient in the PPI group and 0.75 episodes/patient in the non-PPI group (P = 0.01).
CONCLUSIONS
Pre-operative IV pantoprazole administration showed a faster correction of metabolic derangements, and in profound hypochloraemia, the correction occurred substantially faster in the PPI group. Post-operative emesis was significantly less frequent in the PPI group.
Topics: Humans; Pantoprazole; Pyloric Stenosis, Hypertrophic; Retrospective Studies
PubMed: 34916353
DOI: 10.4103/ajps.AJPS_9_21 -
Current Drug Metabolism 2020Cytochrome P450 (CYP450) enzymes play an important role in the metabolism of 70-80% of the currently used medications, including proton pump inhibitors. There are some... (Review)
Review
BACKGROUND
Cytochrome P450 (CYP450) enzymes play an important role in the metabolism of 70-80% of the currently used medications, including proton pump inhibitors. There are some data analyzing the impact of gene polymorphisms of CYP450 enzymes on most widely used PPIs, such as omeprazole, however, the data on pantoprazole are highly lacking.
OBJECTIVE
To summarize the most recent publications and studies on the role of polymorphisms of the genes encoding CYP450 enzyme 2C19 in the metabolism of pantoprazole and pantoprazole based Helicobacter pylori eradication regimens.
METHODS
We performed a non-systematic search of the available literature on the selected topic.
RESULTS AND CONCLUSION
The data on cytochrome P450 gene polymorphisms and their role in pantoprazole metabolism and pantoprazole based Helicobacter pylori eradication remain conflicting. Individual differences in pantoprazole metabolism might be partly related to genetic polymorphisms of CYP450 enzymes. Most of the studies support the observation that cytochrome 2C19 polymorphisms have an impact on the pharmacokinetics of pantoprazole and its therapeutic effects: poor metabolizers of PPIs are more likely to have a better response to pantoprazole therapy and achieve better H. pylori eradication rates compared to rapid metabolizers. The determination of alleles that are associated with decreased (e.g., *2, *3 alleles) or increased (e.g., *17 allele) cytochrome 2C19 enzyme activity might be used as predictive factors for the potential of acid suppression and the success of Helicobacter pylori eradication. Overall, currently available data do not provide robust evidence, therefore, the application of genetic polymorphisms of cytochrome enzymes in clinical practice still cannot be recommended as routine practice for personalized pantoprazole prescription strategies.
Topics: Cytochrome P-450 CYP2C19; Helicobacter Infections; Humans; Pantoprazole; Polymorphism, Genetic; Proton Pump Inhibitors
PubMed: 32407266
DOI: 10.2174/1389200221666200514081442 -
The Annals of Pharmacotherapy Mar 2017Microscopic colitis (MC) is a chronic inflammatory disease of the colon that is characterized by chronic, watery, nonbloody diarrhea. Concern regarding a potential... (Review)
Review
OBJECTIVE
Microscopic colitis (MC) is a chronic inflammatory disease of the colon that is characterized by chronic, watery, nonbloody diarrhea. Concern regarding a potential association between proton-pump inhibitors (PPIs) and MC has recently emerged. We sought to systematically review and summarize the evidence for the potential association between PPIs and MC.
DATA SOURCES
We systematically searched EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, and Google Scholar using the terms proton-pump inhibitors (omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, or esomeprazole), microscopic colitis, collagenous colitis, and lymphocytic colitis.
STUDY SELECTION
Full-text, English-language reports of case reports/series, observational studies, experimental studies, and systematic reviews/meta-analyses published between January 2000 to August 2016 were included. Bibliographies from pertinent publications were reviewed for additional references. Outcome was defined as the development of biopsy-confirmed MC.
DATA EXTRACTION/SYNTHESIS
A total of 19 publications were identified: 5 case control studies and 14 case reports/series (encompassing a total of 32 cases). All studies were limited by small sample sizes. Risk of MC by dose or specific PPI agent was not investigated in any of the studies. A review of the current body of evidence reveals a possible association between PPIs and MC.
CONCLUSIONS
There is a need for large observational studies of high quality to examine the differential effect of specific PPIs and whether the magnitude of association is dose dependent. Given their widespread use, clinicians should routinely question whether patients are receiving unnecessary treatment with PPIs and discontinue therapy where appropriate.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Colitis, Microscopic; Dose-Response Relationship, Drug; Esomeprazole; Humans; Omeprazole; Pantoprazole; Practice Guidelines as Topic; Proton Pump Inhibitors
PubMed: 27733667
DOI: 10.1177/1060028016673859 -
Clinical Pharmacology in Drug... May 2021This study aimed to evaluate the bioequivalence of 2 pantoprazole sodium enteric-coated tablet formulations, a generic formulation and a branded formulation, and to... (Comparative Study)
Comparative Study Randomized Controlled Trial
This study aimed to evaluate the bioequivalence of 2 pantoprazole sodium enteric-coated tablet formulations, a generic formulation and a branded formulation, and to investigate their pharmacokinetic and safety profiles. The study was designed as a single-center, randomized, open-label, single-dose, dual-period, and 2-sequence crossover trial, and was divided into fasting and postprandial human bioequivalence trials. In the first trial, 36 subjects were fasted overnight before they were given generic or branded tablets (during 2 separate administration periods). Separately, 42 subjects were provided a high-fat meal 1 hour before the drugs were administered. Blood specimens of each subject were obtained up to 24 hours after drug administration. No significant differences were observed between the pharmacokinetic profiles of the generic and branded pantoprazole sodium enteric-coated tablets. Bioequivalence was evaluated using 90% confidence intervals for the ratio of test/reference log area under the concentration-time curve over 24 hours, log area under the concentration-time curve to infinity (AUC ), and log peak concentration (C ). The 90% confidence intervals of the least squares geometric mean ratio of C , area under the concentration-time curve from time zero to the last measurable concentration (AUC ), and AUC of 36 subjects in the fasting trial and of 40 of 41 subjects in the postprandial trial (C [41], AUC [41], and AUC [40]) were in accordance with the bioequivalence criteria. No severe adverse effects were detected. The generic and branded pantoprazole sodium enteric-coated tablets were considered bioequivalent with similar safety profiles.
Topics: Adult; Area Under Curve; Cross-Over Studies; Drugs, Generic; Fasting; Female; Food-Drug Interactions; Humans; Male; Pantoprazole; Proton Pump Inhibitors; Tablets, Enteric-Coated; Therapeutic Equivalency; Young Adult
PubMed: 33128847
DOI: 10.1002/cpdd.888