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Endocrine, Metabolic & Immune Disorders... Feb 2023Prenatal period is a critical developmental phase that is sensitive to hormonal disruption by natural and/or exogenous hormones. Some pharmaceuticals frequently...
BACKGROUND
Prenatal period is a critical developmental phase that is sensitive to hormonal disruption by natural and/or exogenous hormones. Some pharmaceuticals frequently prescribed and used safely during pregnancy are shown to interact with the developmental programming of fetus, resulting in endocrine-related adverse effects.
OBJECTIVE
In this research, we aimed to determine the endocrine disrupting potential of paracetamol, indomethacin, alpha-methyldopa and pantoprazole which are frequently prescribed pharmaceuticals during pregnancy.
METHODS
In vitro aromatase inhibitory, estrogen receptor (ER) agonist/antagonist (E-Screen assay) and hormone biosynthesis modulatory effects (H295R steroidogenesis assay) of the selected pharmaceuticals were evaluated. Furthermore, their effects on viability of MCF-7/BUS and H295R cells were also evaluated by MTT assay.
RESULTS
None of the pharmaceuticals affected H295R cell viability. Only indomethacin reduced MCF-7/BUS cell viability at 100µM and 300µM. Among the tested pharmaceuticals, only paracetamol and indomethacin showed aromatase inhibitory activity with IC 50 values of 14.7 x 10 -5 M and 57.6 x 10 -5 M, respectively. Moreover, indomethacin displayed a biphasic ER agonist effect. ER antagonist effects of indomethacin and pantoprazole were confirmed by performing two stepped E-Screen assay. After the partial validation of the H295R steroidogenesis assay with forskolin and prochloraz, the effects of pharmaceuticals on synthesis of testosterone (T) and estradiol (E2) levels were tested. Alpha-methyldopa increased E2 at all tested concentrations and T at 1.48 and 4.4µM. Contrarily other tested pharmaceuticals did not affect steroidogenesis.
CONCLUSION
Present data suggest that all tested pharmaceuticals may have potential endocrine disrupting effect, which should be considered when used in pregnancy.
PubMed: 36843259
DOI: 10.2174/1871530323666230224145624 -
International Journal of Molecular... Jan 2023Proton-pump inhibitors (PPI), e.g., omeprazole or pantoprazole, are the most widely used drugs for various gastrointestinal diseases. However, more and more side...
Proton-pump inhibitors (PPI), e.g., omeprazole or pantoprazole, are the most widely used drugs for various gastrointestinal diseases. However, more and more side effects, especially an increased risk of infections, have been reported in recent years. The underlying mechanism has still not yet been fully uncovered. Hence, in this study, we analyzed the T cell response after treatment with pantoprazole in vitro. Pantoprazole preincubation reduced the production and secretion of interferon (IFN)-γ and interleukin (IL)-2 after the T cells were activated with phytohemagglutinin (PHA)-L or toxic shock syndrome toxin-1 (TSST-1). Moreover, a lower zinc concentration in the cytoplasm and a higher concentration in the lysosomes were observed in the pantoprazole-treated group compared to the untreated group. We also tested the expression of the zinc transporter Zrt- and Irt-like protein (Zip)8, which is located in the lysosomal membrane and plays a key role in regulating intracellular zinc distribution after T cell activation. Pantoprazole reduced the expression of Zip8. Furthermore, we measured the expression of cAMP-responsive element modulator (CREM) α, which directly suppresses the expression of IL-2, and the expression of the phosphorylated cAMP response element-binding protein (pCREB), which can promote the expression of IFN-γ. The expression of CREMα was dramatically increased, and different isoforms appeared, whereas the expression of pCREB was downregulated after the T cells were treated with pantoprazole. In conclusion, pantoprazole downregulates IFN-γ and IL-2 expression by regulating the expression of Zip8 and pCREB or CREMα, respectively.
Topics: Proton Pump Inhibitors; Pantoprazole; Interleukin-2; 2-Pyridinylmethylsulfinylbenzimidazoles; Zinc; T-Lymphocytes; Acids
PubMed: 36674704
DOI: 10.3390/ijms24021191 -
Pharmacopsychiatry Mar 2020Polypharmacy including somatic medications such as proton pump inhibitors is a common phenomenon in psychiatric care. The aim of this study was to evaluate the...
BACKGROUND
Polypharmacy including somatic medications such as proton pump inhibitors is a common phenomenon in psychiatric care. The aim of this study was to evaluate the pantoprazole effects on clozapine metabolism.
METHODS
A large therapeutic drug-monitoring database containing plasma concentrations of CLZ was analyzed. The results were stratified into four groups: a non-smoking (n=250) and a smoking group (n=326), and two groups co-medicated with pantoprazole: non-smokers (n=26) and smokers (n=29). The analysis was based on the non-parametrical Mann-Whitney U test (M-W-U) with a significance level of 0.05.
RESULTS
Differences reached statistical significance for pharmacokinetic parameters between CLZ monotherapy and co-medication with pantoprazole neither in smokers nor in non-smokers (p>0.05 for M-W-U in pairwise comparisons). In patients with clozapine monotherapy, smokers had a higher daily dosage of CLZ compared to non-smokers (mean dosage 363±181 vs. 291±145 mg/day, p<0.001 for M-W-U).
CONCLUSIONS
Adding pantoprazole to an ongoing treatment with clozapine does not alter the metabolism of clozapine to a significant extent.
Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Databases, Factual; Drug Interactions; Drug Monitoring; Female; Humans; Male; Middle Aged; Pantoprazole; Proton Pump Inhibitors; Smokers; Young Adult
PubMed: 31614374
DOI: 10.1055/a-1021-8827 -
The Journal of the Association of... Oct 2023: To evaluate the effectiveness of rabeprazole and other proton pump inhibitors (PPIs) in providing symptomatic relief in patients with varying severity of...
: To evaluate the effectiveness of rabeprazole and other proton pump inhibitors (PPIs) in providing symptomatic relief in patients with varying severity of gastroesophageal reflux disease (GERD). : In this multicenter retrospective study, electronic medical records (EMRs) of GERD patients prescribed with PPIs at two Indian clinics/hospitals were reviewed (2016-2020). Rabeprazole's effectiveness was assessed at different follow-up visits and compared with other PPIs. : Overall, 269 patients (moderate and severe GERD: 84.39%) were included in three groups, rabeprazole, pantoprazole, and esomeprazole groups. A significant proportion of patients experienced quick and complete symptomatic relief at visit 1 with rabeprazole compared to the baseline visit, which gradually increased till visit 4 for both daytime [ heartburn (38.78-93.88%; < 0.001)] and nocturnal symptoms [ sleep disturbances (62.92-97.75%; < 0.001)]. Rabeprazole provided quick relief at visit 1 when compared with pantoprazole for daytime heartburn (38.78 vs 5.56%; = 0.01), daytime epigastric pain (66.04 vs 12.12%; = 0.049), and nocturnal water brash (60.71 vs 16.13%; = 0.015), and when compared with esomeprazole for nocturnal nausea (82.61 vs 20.00%; = 0.013). Further, the proportion of patients exhibiting complete treatment response was relatively higher in the rabeprazole group (83.33%) than in the pantoprazole (62.07%) and esomeprazole (65.67%) groups at visit 4. : Rabeprazole was effective in providing quick and sustained relief for both daytime and nocturnal GERD symptoms in patients with moderate and severe GERD. Rabeprazole also demonstrated greater effectiveness when compared with pantoprazole and esomeprazole in reducing the severity of multiple GERD symptoms. : Lawate P, Jilawar N, Vyas K, Effectiveness of Rabeprazole and Other Proton Pump Inhibitors in Managing GERD with Varying Severity: A Retrospective, Real-world EMR-based Study (POWER GERD Study). J Assoc Physicians India 2023;71(10):37-44.
Topics: Humans; Proton Pump Inhibitors; Gastroesophageal Reflux; Rabeprazole; Retrospective Studies; Male; Female; Middle Aged; Severity of Illness Index; Adult; Pantoprazole; Esomeprazole; Treatment Outcome; Electronic Health Records
PubMed: 38716522
DOI: 10.59556/japi.71.0366 -
Indian Journal of Otolaryngology and... Dec 2022To evaluate and compare pre and post treatment results using the following parameters by (a) Dual probe pH monitoring. (b) Laryngeal mucosal changes as assessed by...
To Compare and Evaluate Laryngeal Changes in Patients with Dysphonia in Laryngopharyngeal Reflux (LPR) before and after Treatment with Proton Pump Inhibitors (PPI) and Prokinetic Drugs.
To evaluate and compare pre and post treatment results using the following parameters by (a) Dual probe pH monitoring. (b) Laryngeal mucosal changes as assessed by direct video laryngoscopy/stroboscopy using Belafsky scores. (c) Voice changes by using GRBAS and Dr Speech software for speech analysis. In our study we have evaluated and compared voice and laryngeal changes in patients with dysphonia and RSI > 10 (which is suggestive of LPR) before treatment and after 6 months of treatment with Tab. Pantoprazole and Tab. Mosapride. This prospective study was carried out on 50 patients attending the ENT OPD of a tertiary care referral centre over a period of 18 months i.e. from Nov 2008 to Apr 2010. The study showed that prolonged therapy (> 6 months) is required to treat LPR effectively and 24 h ambulatory dual probe pH metry and videolaryngoscopy to assess RFS are the most preferred diagnostic tools in LPR. Dr Speech software for voice analysis can give an objective assessment of voice changes in LPR before and after treatment. The treatment consisting of PPI and prokinetic drugs proved to be effective in laryngopharyngeal reflux disease as improvement was seen in all the parameters including reflux findings score, subjective and objective voice assessment. According to results of our study, 24 h ambulatory dual probe pH metry, Reflux Finding Score (RFS), subjective and objective acoustic parameters can be used as indicators of efficacy of treatment.
PubMed: 36742570
DOI: 10.1007/s12070-020-02323-9 -
Journal of Veterinary Internal Medicine Mar 2020Upper gastrointestinal (GI) ulceration and bleeding in critically ill dogs can cause severe anemia and increase morbidity. Acid suppressants using proton pump inhibitors...
BACKGROUND
Upper gastrointestinal (GI) ulceration and bleeding in critically ill dogs can cause severe anemia and increase morbidity. Acid suppressants using proton pump inhibitors or histamine-2 receptor blockers administered IV is commonly recommended.
HYPOTHESIS/OBJECTIVES
To evaluate the efficacy of IV administered esomeprazole, pantoprazole, and famotidine constant rate infusion (CRI) on increasing the intragastric pH of dogs. We hypothesized that esomeprazole and famotidine CRI would provide superior acid suppression compared to pantoprazole and reach pH goals for the treatment of GI bleeding.
ANIMALS
Nine healthy research Beagles.
METHODS
Randomized, 3-way crossover. Dogs received pantoprazole or esomeprazole at 1 mg/kg IV q12h and famotidine with a loading dose of 1 mg/kg followed by 8 mg/kg IV CRI daily for 3 consecutive days. The intragastric pH was recorded at baseline and for 72 hours of treatment. The mean pH and the mean percentage time (MPT) the intragastric pH was ≥3 or ≥4 were compared among and within treatment groups.
RESULTS
Significant increases in mean pH (P < 0.0001), MPT ≥3 (P < 0.001), and MPT ≥4 (P = 0.0006) were noted over time with all 3 treatments. The time effect did not differ by treatment for mean pH, MPT ≥3, and MPT ≥4 (P = .29, .56, and .37, respectively); however, only esomeprazole and famotidine CRI achieved the goals established for the treatment of gastroduodenal ulceration in people.
CONCLUSIONS AND CLINICAL IMPORTANCE
Famotidine CRI and esomeprazole might be superior acid suppressants compared to standard doses of pantoprazole for the first 72 hours of treatment.
Topics: Animals; Anti-Ulcer Agents; Cross-Over Studies; Dogs; Esomeprazole; Famotidine; Female; Hydrogen-Ion Concentration; Injections, Intravenous; Male; Pantoprazole
PubMed: 32020689
DOI: 10.1111/jvim.15718 -
Journal of Clinical and Experimental... 2023Up-to-date data about the role of acid suppression therapy e.g. proton-pump inhibitors; to reduce post-endoscopic variceal ligation (EVL) ulcer-bleeding are...
Efficacy of Vonoprazan vs. Pantoprazole or Non-acid Suppression in Prevention of Post-variceal Ligation Ulcer Bleeding in Portal Hypertension: A Multi-arm Randomized Controlled Trial.
BACKGROUND
Up-to-date data about the role of acid suppression therapy e.g. proton-pump inhibitors; to reduce post-endoscopic variceal ligation (EVL) ulcer-bleeding are conflicting. Vonoprazan; a recently introduced potassium-competitor acid blocker, has not been studied to prevent post-EVL ulcer/bleeding. The aim was to evaluate the efficacy of vonoprazan vs. pantoprazole or non-acid suppression to prevent post-EVL ulcer/bleeding in portal hypertension patients.
MATERIAL AND METHODS
We enrolled 275 portal hypertension patients undergoing EVL in a three-arm randomized, single-blind, controlled study. A clinico-laboratory baseline evaluation was performed. Following EVL, patients were randomly and equally assigned to receive vonoprazan 20mg once daily, pantoprazole 40 mg once daily, or no acid suppression therapy. Post-EVL ulcer bleeding, ulcer dimensions, odynophagia as well as vonoprazan safety were evaluated after 2 weeks of EVL.
RESULTS
Post-EVL ulcer bleeding occurred among 2.15% of vonoprazan, 8.7% of pantoprazole, and 14.2% of the non-acid suppression groups ( < 0.001). Post-ligation ulcer frequency and dimensions were higher among non-acid suppression and pantoprazole groups vs. vonoprazan ( < 0.05). Chest pain and odynophagia were encountered among 73.6% and 54.9% of the non-acid suppression group vs. 39.6% and 45.1% in pantoprazole, and 17.2% and 21.5% in vonoprazan groups, respectively ( < 0.05). There were no vonoprazan-related adverse events. Non-use of vonoprazan was the strongest independent predictor for post-EVL bleeding.
CONCLUSION
Short course of vonoprazan 20 mg/day is safe and superior to pantoprazole 40 mg/day in the reduction of post-EVL ulcer dimensions at 2 weeks post-EVL, and prevention of ulcer-related bleeding. Acid suppression is superior to no acid suppression to prevent post-EVL complications.
PubMed: 37975046
DOI: 10.1016/j.jceh.2023.05.008 -
Journal of Pharmaceutical and... Sep 2020X-ray is used in several areas for analysis, imaging, sterilisation and security. X-ray machines are increasingly used in the entrance of the airports, shopping centres,...
X-ray is used in several areas for analysis, imaging, sterilisation and security. X-ray machines are increasingly used in the entrance of the airports, shopping centres, etc. for security purposes. Therefore, human beings and belongings are frequently exposed to X-ray by transiting these checkpoints at various sites such as airports, shopping centres etc. This study aims is to investigate the X-rays potential effects (arising from security machines) on different groups of medicines which are analgesics (acetaminophen, acetylsalicylic acid, naproxen, flurbiprofen), anti-diabetics (metformin HCl, pioglitazone), PPI's (lansoprazole, pantoprazole sesquihydrate), anti-hypertensives (losartan, clopidogrel hydrogen sulphate), heart failure medicines (verapamil HCl, spironolactone) used frequently and daily, by using ESR analysis. Coated acetylsalicylic acid tablets showed different intensities of ESR signals after 58 mGy irradiation. It thought to be the result of the coating polymer (Hydroxypropylmethylcellulose (HPMC)). According to the ESR results which were obtained for 0,24-58 mGy irradiated drugs- 1 hour after irradiation (refrigerated during this period) X-ray did not affect those medicines except the acetylsalicylic acid tablets significantly. The meaningful differences were only obtained between the non-irradiated, and 58 mGy irradiated acetylsalicylic acid tablets. Therefore, it can be concluded that X-ray exposed medicines, except coated acetylsalicylic acid tablets (after 58 mGy irradiation), can be used safely for the irradiation levels used in this study (0.24 mGy-0.58 mGy). In addition those data, ESR analyses were followed by other analysis such as FT-IR, DSC/TGA, dissolution, SEM, etc., and they are planned to be published soon.
Topics: Acetaminophen; Humans; Hypromellose Derivatives; Spectroscopy, Fourier Transform Infrared; Tablets; X-Rays
PubMed: 32534404
DOI: 10.1016/j.jpba.2020.113311 -
Clinical Pharmacology in Drug... Feb 2022Hydroxychloroquine as a weak basic compound with two amines is strongly enriched in cell compartments with low pH, suggesting that modification of gastric pH by... (Randomized Controlled Trial)
Randomized Controlled Trial
Hydroxychloroquine as a weak basic compound with two amines is strongly enriched in cell compartments with low pH, suggesting that modification of gastric pH by coadministered proton pump inhibitors might reduce its solubility and absorption and thus its efficacy in patients. We addressed this question in a single-center, open-label, randomized, parallel drug-drug interaction trial in healthy adults (EudraCT No. 2020-001470-30). All participants received a single oral dose of 400-mg hydroxychloroquine, and one group additionally received 40 mg of pantoprazole once daily for 9 days dosed to steady state. Whole-blood samples were collected for 72 hours, and hydroxychloroquine was quantified by liquid chromatography-tandem mass spectrometry. Primary endpoints were whole-blood hydroxychloroquine areas under the concentration-time curve from 0 to 72 hours (AUC ) and peak concentrations (C ). Unpaired 2-sided t-tests of the log transformed pharmacokinetic parameters were performed to compare both groups. Twenty-four participants (12 per group) were included. Hydroxychloroquine AUC and C did not differ between groups without and with pantoprazole (arithmetic mean; AUC , 7649 ng/ml • h, and 8429 ng/ml • h, P = .50; C , 448 ng/mL and 451.5 ng/mL, P = .96, respectively). Pantoprazole did not alter hydroxychloroquine absorption, indicating that proton pump inhibitors do not affect its bioavailability.
Topics: Adult; Biological Availability; Chromatography, Liquid; Drug Interactions; Humans; Pantoprazole; Proton Pump Inhibitors
PubMed: 34268908
DOI: 10.1002/cpdd.999 -
American Journal of Therapeutics Apr 2021
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Granuloma; Humans; Kidney; Nephritis, Interstitial; Pantoprazole
PubMed: 33852474
DOI: 10.1097/MJT.0000000000001368