-
Frontiers in Psychiatry 2023QT prolongation carries the risk of ventricular tachyarrhythmia (Torsades de Pointes) and sudden cardiac death. Psychotropic drugs can affect ventricular repolarization...
INTRODUCTION
QT prolongation carries the risk of ventricular tachyarrhythmia (Torsades de Pointes) and sudden cardiac death. Psychotropic drugs can affect ventricular repolarization and thus prolong the QT interval. The present study sought to investigate the risk factors (pharmacological and non-pharmacological) of severe QT prolongation in gerontopsychiatric patients.
METHODS
Electrocardiograms of patients on a gerontopsychiatric ward were screened for QT prolongation. Medication lists were examined utilizing the AzCERT classification. Potential drug interactions were identified with the electronic drug interaction program mediQ.
RESULTS
The overall prevalence of QT prolongation was 13.6%, with 1.9% displaying severe QT prolongation (≥ 500 ms). No statistically significant differences between patients with moderate and severe QT prolongation were identified; however, patients with severe QT prolongation tended to take more drugs ( = 0.063). 92.7% of patients with QT prolongation took at least one AzCERT-listed drug, most frequently risperidone and pantoprazole. Risperidone and pantoprazole, along with pipamperone, were also most frequently involved in potential drug interactions. All patients displayed additional risk factors for QT prolongation, particularly cardiac diseases.
CONCLUSION
In addition to the use of potentially QT-prolonging drugs, other risk factors, especially cardiac diseases, appear to be relevant for the development of QT prolongation in gerontopsychiatric patients. Pantoprazole was frequently involved in potential drug interactions and should generally not be used for more than 8 weeks in geriatric populations. As clinical consequences of QT prolongation were rare, potentially QT-prolonging drugs should not be used overcautiously; their therapeutic benefit should be considered as well. It is paramount to perform diligent benefit-risk analyses prior to the initiation of potentially QT-prolonging drugs and to closely monitor their clinical (side) effects.
PubMed: 37032947
DOI: 10.3389/fpsyt.2023.1157996 -
European Journal of Clinical... Mar 2018The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of S-(-)-pantoprazole (PPZ) sodium injections following single and... (Clinical Trial)
Clinical Trial Comparative Study
PURPOSE
The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of S-(-)-pantoprazole (PPZ) sodium injections following single and multiple intravenous doses in healthy Chinese subjects.
METHODS
The dosage groups were set as followed: 20 mg of single and multiple intravenous administration of S-(-)-PPZ, 40 mg of single and multiple intravenous administration of S-(-)-PPZ or pantoprazole, and 80 mg of single dosage group of S-(-)-PPZ. Subjects were sampled for pharmacokinetic analysis and were monitored for 24-h intragastric pH prior to and 48-h intragastric pH after administration for the pharmacodynamic study. The pharmacokinetic and pharmacodynamic parameters were compared between S-(-)-PPZ and PPZ. Safety was evaluated on the basis of adverse events, vital signs, laboratory tests, and physical examination.
RESULTS
All adverse events were mild and of limited duration. Maximum plasma concentration and area under the concentration-time curve for S-(-)-PPZ were dose proportional over the range of 20-80 mg following a single intravenous administration. Elimination rate constant and half-life observed statistical difference from a single dose to multiple doses in 40 mg of S-(-)-PPZ groups. After administration of a single dose, the mean 24-h intragastric pH value was observed higher in 80-mg group than in 40- and 20-mg groups. Slightly increase of intragastric pH was found after a single dose of 40 mg S-(-)-PPZ than 40 mg PPZ; however, the differences were not statistically significant.
CONCLUSIONS
Twice daily of 40 mg S-(-)-PPZ sodium injections is effective in achieving satisfying acid inhibition. Compared with plasma R-(+)-PPZ levels, most subjects presented more potent and prolonged suppression of gastric acid of S-(-)-PPZ, while a few subjects showed faster metabolic rate of S-(-)-PPZ in vivo.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Area Under Curve; China; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Compounding; Female; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Half-Life; Humans; Injections, Intravenous; Male; Metabolic Clearance Rate; Monitoring, Ambulatory; Pantoprazole; Proton Pump Inhibitors; Reproducibility of Results; Stereoisomerism; Young Adult
PubMed: 29167917
DOI: 10.1007/s00228-017-2372-6 -
American Journal of Translational... 2021To investigate the protective effect of teprenone on gastric mucosal injury induced by dual antiplatelet therapy in rats.
OBJECTIVE
To investigate the protective effect of teprenone on gastric mucosal injury induced by dual antiplatelet therapy in rats.
METHODS
Healthy, specifically pathogen free SD, rats were selected and divided into 4 groups: Normal group (normal rats, without any treatment), Model group (rats received dual antiplatelet therapy: aspirin and clopidogrel), Teprenone group (rats received dual antiplatelet therapy and teprenone) and Pantoprazole group (rats received dual antiplatelet therapy and pantoprazole). The gastric mucosal blood flow, ulcer index, gastric gel mucus thickness, the levels of gastrin (Gas), prostaglandin (PG), prostaglandin E (PGE), endothelin-1 (ET-1) tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 in serum, the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and myeloperoxidase (MPO) in the gastric mucosa, as well as the expression of vascular endothelial growth factor (VEGF) in the rat's stomach were measured.
RESULTS
Compared with the Normal group, the other groups showed more severe gastric injury, elevated levels of inflammatory factors (TNF-α, IL-1β, IL-6 and IL-10), elevated levels of MDA and MPO, as well as reduced levels of GSH, SOD and VEGF (all P<0.05). Compared with the Model group, the gastric mucosal lesions in the Teprenone group and the Pantoprazole group were improved significantly (both P<0.05). Compared with the Pantoprazole group, the Teprenone group had reduced levels of ET-1 and elevated levels of PG and PGE (all P<0.05).
CONCLUSION
Teprenone protects against gastric mucosal injury induced by dual antiplatelet therapy through inhibiting gastric mucosal inflammation inhibiting oxidative stress and improving gastric mucosa indices.
PubMed: 34017431
DOI: No ID Found -
Andrology Nov 2020The effects of PPIs on human sperm fertilizing capacity were poorly investigated although these drugs are widely over-used. Two publications retrospectively studied...
BACKGROUND
The effects of PPIs on human sperm fertilizing capacity were poorly investigated although these drugs are widely over-used. Two publications retrospectively studied relationships between any PPI intake and sperm parameters from patients consulting at infertility clinics, but the conclusions of these reports were contradictory. Only two reports investigated the effects of lansoprazole and omeprazole on sperm motility and found lansoprazole to be deleterious and omeprazole to be neutral for sperm motility. The inconsistency of the PPI effect in the previous reports emphasizes the need for more basic research on human spermatozoa, taking into account the hypothesis that the different PPI drugs may have different effects on sperm physiology.
OBJECTIVES
Do PPIs, which are among the most widely sold drug in the word, impact negatively human sperm capacitation and sperm motility?
MATERIALS AND METHODS
The effects of PPIs on human sperm maturation and motility were analyzed by CASA, flow cytometry, and Western blot.
RESULTS
We tested the impact of 6 different PPIs on human sperm motility and capacitation. We showed that pantoprazole, but not the other PPIs, decreased sperm progressive motility and capacitation-induced sperm hyperactivation. We therefore investigated further the effects of pantoprazole on sperm capacitation, and we observed that it had a significant deleterious effect on the capacitation-induced hyperpolarization of the membrane potential and capacitation-associated protein phosphorylation.
DISCUSSION AND CONCLUSION
Our results indicate that exposure to pantoprazole has an adverse effect on the physiological competence of human spermatozoa. As the capacitation process takes place within the female tract, our results suggest that PPIs intake by the female partner may impair in vivo sperm maturation and possibly fertilization. Moreover, the absence of adverse effect by PPIs on mouse sperm emphasizes the need to develop reprotox assays using human material to better assess the effects of medication intake on sperm physiology.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Fertilization; Humans; Lansoprazole; Male; Membrane Potentials; Middle Aged; Omeprazole; Pantoprazole; Phosphorylation; Proton Pump Inhibitors; Rabeprazole; Retrospective Studies; Semen Analysis; Sperm Capacitation; Sperm Maturation; Sperm Motility; Spermatozoa; Young Adult
PubMed: 32609951
DOI: 10.1111/andr.12855 -
Medical Oncology (Northwood, London,... Dec 2023Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to... (Randomized Controlled Trial)
Randomized Controlled Trial
Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to cytotoxic therapy. We conducted a phase I/II randomized controlled trial in adult patients with head and neck squamous cell carcinoma (HNSCC) planned for first-line palliative chemotherapy. Patients were randomized to chemotherapy + / - intravenous (IV) pantoprazole. The primary endpoint in phase I was to determine the maximum safe dose of intravenous pantoprazole, whereas it was progression-free survival (PFS) in phase II. The dose of IV pantoprazole established in phase I was 240 mg. Between Nov'18 and Oct'20, we recruited 120 patients in phase II, 59 on pantoprazole and 61 on the standard arm. Median age was 51 years (IQR 43-60), 80% were men. Systemic therapy was IV cisplatin in 22% and oral-metronomic-chemotherapy (OMC) in 78%. Addition of pantoprazole did not prolong PFS, which was 2.2 months (95% CI 2.07-3.19) in the pantoprazole arm and 2.5 months (95% CI 2.04-3.81, HR, 1.14; 95% CI 0.78-1.66; P = 0.48) in the standard arm. Response rates were similar; pantoprazole arm 8.5%, standard arm 6.6%; P = 0.175. Overall survival was also similar; 5.6 months (95% CI 4.47-8.51) in the pantoprazole arm and 5.4 months (95% CI 3.48-8.54, HR 1.06; 95% CI 0.72-1.57; P = 0.75) in the standard arm. Grade ≥ 3 toxicities were similar. Thus, pantoprazole 240 mg IV added to systemic therapy does not improve outcomes in patients with advanced HNSCC.
Topics: Adult; Male; Humans; Middle Aged; Female; Squamous Cell Carcinoma of Head and Neck; Pantoprazole; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Cisplatin; Antineoplastic Combined Chemotherapy Protocols; Tumor Microenvironment
PubMed: 38129716
DOI: 10.1007/s12032-023-02234-z -
Advances in Therapy Aug 2020Dabigatran is a direct oral anticoagulant (DOAC) used for the treatment of several thrombotic conditions. To date, very few pharmacogenetic studies on dabigatran were... (Comparative Study)
Comparative Study
INTRODUCTION
Dabigatran is a direct oral anticoagulant (DOAC) used for the treatment of several thrombotic conditions. To date, very few pharmacogenetic studies on dabigatran were published. We aimed to investigate the influence of 59 polymorphisms in 15 genes (including CES1, UGT and CYP that encode enzymes and ABCB1 and SLC that encode transporters), concomitant treatment with pantoprazole and demographic characteristics (including sex or race) on dabigatran pharmacokinetics and safety.
METHODS
This was a candidate gene pharmacogenetic study. The study population comprised 107 volunteers enrolled in two dabigatran bioequivalence clinical trials; they were genotyped with a ThermoFisher QuantStudio 12K Flex OpenArray instrument. SPSS software v.21 was used for statistical analysis.
RESULTS
Women showed a higher exposure to dabigatran compared to men. The concomitant treatment with pantoprazole was associated with a decreased exposure to the drug. CYP2D6 poor metabolizers (PMs) were related to lower clearance (Cl/F) (p = 0.049) and a tendency was observed towards higher area under the curve (AUC), maximum concentration (C) and to lower volume of distribution (V/F) (p < 0.10). SLC22A1 haplotype was related to pharmacokinetic variability (p < 0.05). The remaining genes (including CYP, UGT1A1 and ABCB1) had no effect on dabigatran pharmacokinetics (p > 0.10). Women showed more adverse drug reactions (ADR) compared to men (0.40 ± 0.68 vs 0.15 ± 0.41 ADR per person, p = 0.03) and SLC22A1 mutant haplotype was related to a lower risk of nausea (p = 0.02).
CONCLUSION
Sex, concomitant use of pantoprazole and SLC22A1, CYP2D6 and CYP3A5 polymorphism had an effect on dabigatran pharmacokinetics and safety. Previously published pharmacogenetic predictors, namely CES1 or ABCB1 polymorphisms, had no effect on pharmacokinetics and safety. This study is of interest as it increases the scarce pharmacogenetic information on dabigatran.
Topics: ATP Binding Cassette Transporter, Subfamily B; Adolescent; Adult; Anticoagulants; Antithrombins; Area Under Curve; Carboxylic Ester Hydrolases; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Dabigatran; Female; Genotype; Humans; Male; Middle Aged; Organic Cation Transporter 1; Pantoprazole; Pharmacogenetics; Polymorphism, Genetic; Proton Pump Inhibitors; Sex Factors; Spain; Thrombosis; Young Adult
PubMed: 32564268
DOI: 10.1007/s12325-020-01414-x -
Biomedicine & Pharmacotherapy =... Aug 2018Proton pump inhibitors (PPIs) are effective antagonists of gastric acid secretion used to treat a number of gastro-esophageal disorders. The present study investigated...
BACKGROUND AND AIMS
Proton pump inhibitors (PPIs) are effective antagonists of gastric acid secretion used to treat a number of gastro-esophageal disorders. The present study investigated the effect of Pantoprazole on vascular relaxation in-vitro and ex-vivo and its effect on blood coagulation in an animal model.
MAIN METHODS
Isolated mouse arterial rings were pre-contracted in-vitro with phenylephrine and concentration-response curves to the acetylcholine relaxing effect were constructed in the presence of escalating concentrations of pantoprazole. In another set of experiments, male albino mice weighing ∼25 g were administered a daily dose of pantoprazole (0.4 mg by oral gavage) for four consecutive weeks; a vehicle control group was run in parallel. At the end of the treatment period, thoracic aorta was isolated for the assessment of vascular function ex-vivo. Blood samples were also collected to evaluate the effect of chronic pantoprazole therapy on coagulation parameters, namely, prothrombin time (PT) and activated partial thromboplastin time (aPTT).
KEY FINDINGS
Vascular responsiveness to acetylcholine demonstrated a reduced relaxation of the arterial ring from baseline in the presence of different concentrations of pantoprazole (1 μM: 54.69 ± 1.42%, 10 μM: 34.64 ± 0.90% and 100 μM: 31.50 ± 0.67% vs. control 74.39 ± 1.426%, p < 0.001). Furthermore, acetylcholine-induced relaxation of the aorta was significantly diminished after four weeks of administrating pantoprazole to mice (37.12 ± 2.50%) compared with the control group (72.47 ± 1.68%, p < 0.001). This, however, wasn't accompanied by significant changes in the phenylephrine-induced vasoconstriction. Animals that received pantoprazole daily for four weeks also exhibited increased blood coagulation time in comparison to the vehicle control group (PT 45.30 ± 3.52 s vs. 15.30 ± 0.70 s, p < 0.05; aPTT 96.1 ± 4.62 s vs. 48 ± 1.97 s, p < 0.05, respectively).
SIGNIFICANCE
The results of the present investigation suggest that pantoprazole reduces arterial relaxation and interferes with blood coagulation. Additional studies are warranted to assess the clinical implications of such observations.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetylcholine; Animals; Aorta; Blood Coagulation; Disease Models, Animal; Male; Mice; Mice, Inbred BALB C; Pantoprazole; Partial Thromboplastin Time; Phenylephrine; Vasodilation; Vasodilator Agents
PubMed: 29803168
DOI: 10.1016/j.biopha.2018.05.084 -
Clinical and Experimental Dental... Oct 2022Proton pump inhibitors, such as omeprazole and pantoprazole, are frequently prescribed for the treatment of acid reflux. However, those medications have been shown to... (Review)
Review
OBJECTIVES
Proton pump inhibitors, such as omeprazole and pantoprazole, are frequently prescribed for the treatment of acid reflux. However, those medications have been shown to affect a variety of physiologic processes, including bone homeostasis and the gastrointestinal microbiome. The objective of this study was to assess the relationship between proton pump inhibitors and attachment levels around teeth and dental implants. A scoping review was performed to assess the extent and quality of the relevant literature.
MATERIALS AND METHODS
We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) and searched four relevant biomedical literature databases in addition to the grey literature. Keywords in the title and abstract fields, and subject headings for proton pump inhibitors, teeth, and dental implants were included as search terms.
RESULTS
Overall search results identified 791 publications which, after applying the inclusion and exclusion criteria, yielded 27 publications that were further analyzed for relevance and quality of scientific evidence. The majority of eligible publications were retrospective cohort studies. Following critical analysis, 13 publications, including six abstracts, were used to assess the effect of proton pump inhibitors on tissue attachment around teeth and dental implants.
CONCLUSIONS
There are few high-quality studies describing the effect of proton pump inhibitors on tissue attachment around teeth and dental implants. Nevertheless, among the included papers with the fewest confounding factors, there was a positive relationship between proton pump inhibitors and soft tissue attachment levels around teeth, and a predominantly negative but variable effect of proton pump inhibitors on the bone level around dental implants. Additional well-controlled prospective studies are required to fully elucidate those relationships.
Topics: Dental Implants; Humans; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Retrospective Studies
PubMed: 35799099
DOI: 10.1002/cre2.616 -
Toxicology Letters Oct 2020Proton pump inhibitors (PPIs) have wide pleiotropic action in addition to their therapeutic potential in gastroesophageal reflux diseases. Conversely, recent reports...
Proton pump inhibitors (PPIs) have wide pleiotropic action in addition to their therapeutic potential in gastroesophageal reflux diseases. Conversely, recent reports revealed a significant incidence of toxic events of PPIs including nephritis, osteoporosis, and cardiac damage. Thus, the study was designed to reconcile the deceptive contraindications. The present investigation targeted to reveal the toxic impact of sub-acute and sub-chronic administration of pantoprazole (PPZ) with different concentrations (low dose 4 mg/kg, medium-dose 8 mg/kg and high dose 16 mg/kg once a day) on normal vascular endothelium and renal tissue of rats. Vascular endothelial dysfunction (VED) was estimated by the contractility of an isolated aortic ring, nitrite/nitrate concentration, oxidative stress, and integrity of the endothelium layer. Moreover, the renal abnormalities were further confirmed by an increased level of serum creatinine, blood urea nitrogen (BUN), the incidence of microproteinuria, and structural alteration. Sub-acute administration of PPZ treatment did not produce any toxicological impact on endothelium and renal tissue. Whereas, sub-chronic administration of PPZ treatment causes moderate VED and renal dysfunction in a dose-dependent manner. Sub-chronic treatment of PPZ also influences the mitigation of NO and elevation of oxidative stress. Collecting all the evidence, it concludes that decreased nitric oxide availability and increased levels of oxidative stress may be a possible underlying mechanism of causing VED and renal abnormalities from high-dose PPZ treatment.
Topics: Administration, Oral; Animals; Aorta, Thoracic; Cytokines; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Kidney; Lipid Peroxidation; Male; Nitrates; Nitrites; Pantoprazole; Proton Pump Inhibitors; Rats; Rats, Wistar; Vasodilation
PubMed: 32763312
DOI: 10.1016/j.toxlet.2020.07.031 -
Clinical Pharmacology in Drug... Oct 2022Ripretinib is a switch control KIT kinase inhibitor approved for treatment of adults with advanced gastrointestinal stromal tumors who received prior treatment with 3 or...
Ripretinib is a switch control KIT kinase inhibitor approved for treatment of adults with advanced gastrointestinal stromal tumors who received prior treatment with 3 or more kinase inhibitors, including imatinib. Ripretinib and its active metabolite (DP-5439) are cleared mainly via cytochrome P450 enzyme 3A4/5 (CYP3A4/5), and ripretinib solubility is pH-dependent, thus the drug-drug interaction potentials of ripretinib with itraconazole (strong CYP3A inhibitor), rifampin (strong CYP3A inducer), and pantoprazole (proton pump inhibitor) were each evaluated in open-label, fixed-sequence study designs. Overall, 20 participants received ripretinib 50 mg alone and with itraconazole 200 mg once daily, 24 participants received ripretinib 100 mg alone and with rifampin 600 mg once daily, and 25 participants received ripretinib 50 mg alone and with pantoprazole 40 mg once daily. Ripretinib exposure increased with concomitant itraconazole, with geometric least-squares (LS) mean ratios of ripretinib area under the concentration-time curve from 0 to ∞ (AUC ) and maximum observed concentration (C ) of 199% and 136%. Ripretinib exposure decreased with concomitant rifampin: geometric LS mean ratios for ripretinib AUC and C were 39% and 82%. Pantoprazole coadministration had no effect on ripretinib pharmacokinetics. No unexpected safety signals occurred. No dose adjustment is required for ripretinib coadministered with gastric acid reducers and strong CYP3A inhibitors; patients also receiving strong CYP3A inhibitors should be monitored more frequently for adverse reactions. Concomitant ripretinib use with strong CYP3A inducers should be avoided. Prescribers should refer to approved labeling for specific dose recommendations with concomitant use of strong and moderate CYP3A inducers.
Topics: Adult; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Drug Therapy, Combination; Gastric Acid; Humans; Imatinib Mesylate; Itraconazole; Naphthyridines; Pantoprazole; Protein Kinase Inhibitors; Proton Pump Inhibitors; Rifampin; Urea
PubMed: 35560823
DOI: 10.1002/cpdd.1110