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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 -
Journal of the American Society of... Jul 2024
Observational Study Randomized Controlled Trial
Topics: Humans; Pantoprazole; Proton Pump Inhibitors; Male; Female; Aged; Middle Aged; Glomerular Filtration Rate; Treatment Outcome
PubMed: 38602780
DOI: 10.1681/ASN.0000000000000356 -
Biomacromolecules Nov 2022Here, we describe an intracellular pH-regulating nanoparticle (IPRN), coencapsulated with chemosensitizers and anticancer agents for effective and safe cancer treatment....
Here, we describe an intracellular pH-regulating nanoparticle (IPRN), coencapsulated with chemosensitizers and anticancer agents for effective and safe cancer treatment. IPRN contains a tubulysin derivative (TUB), a hydrophobic anticancer drug, and pantoprazole (PTZ), a hydrophilic proton-pump inhibitor. IPRN with a size of 62 nm has an anionic surface charge and is stable for at least two weeks under storage conditions, though PTZ and TUB encapsulated in IPRN showed different drug release patterns. PTZ was released before TUB, controlling the cancer's intracellular pH, maintaining a pH at which TUB can work well. The encapsulated PTZ increased the pH of endolysosomes and inhibited ion trapping, with TUB ionization, thereby exhibiting increased cytotoxicity compared with free TUB observed in various cancer cell lines, such as human liver adenocarcinoma, human glioblastoma, and human pancreatic carcinoma. IPRN exhibited a 1.9-fold improved tumor growth inhibitory effect in a human liver adenocarcinoma-bearing mouse model, while minimizing the hepatotoxicity of free TUB. Thus, nanomedicines that contain both a chemosensitizer and an anticancer agent, such as IPRN, are expected to be next-generation anticancer agents that reduce the side effects of anticancer drugs and increase the therapeutic effect.
Topics: Mice; Animals; Humans; Nanoparticles; Hydrogen-Ion Concentration; Antineoplastic Agents; Liver Neoplasms; Adenocarcinoma; Drug Carriers; Cell Line, Tumor
PubMed: 36223489
DOI: 10.1021/acs.biomac.2c00952 -
Experimental and Therapeutic Medicine Jun 2023The present network meta-analysis aimed to enhance the corresponding evidence with respect to the efficacy and safety of pharmaceuticals treatments. Frequentist network...
The present network meta-analysis aimed to enhance the corresponding evidence with respect to the efficacy and safety of pharmaceuticals treatments. Frequentist network meta-analysis was used. Medical literature up to November 2022 was searched for randomized clinical trials assessing the efficacy and safety of these pharmaceuticals, either compared with each other or compared with placebo. With the exception of ranitidine (300 mg four times daily) and vonoprazan (20 mg once daily) having lower safety than placebo, the efficacy and safety of the remaining treatments were superior to placebo. Cimetidine (400 mg four times daily) and pantoprazole (40 mg once daily) were ranked first in terms of efficacy. The frequentist network meta-analysis shows that for cimetidine (except 400 mg once daily), famotidine, rabeprazole, ilaprazole, lansoprazole (except 7.5 mg once daily) and omeprazole (except 10 mg once daily or 30 mg once daily), the efficacy comparison between the different doses of each of the aforementioned pharmaceuticals did not indicate statistically significant differences. In conclusion, pantoprazole (40 mg once daily) was the best choice for the initial non-eradication treatment of patients with duodenal ulcer, and cimetidine (400 mg twice daily), omeprazole (20 mg once daily), lansoprazole (15 mg once daily), ilaprazole (5 mg once daily) and rabeprazole (10 mg once daily) could be used as the first choice. If the aforementioned pharmaceuticals cannot be prescribed, famotidine (40 mg twice daily) is recommended.
PubMed: 37206569
DOI: 10.3892/etm.2023.11971 -
Journal of the American Medical... Dec 2022Thoughtful integration of interruptive clinical decision support (CDS) alerts within the electronic health record is essential to guide clinicians on the application of...
Thoughtful integration of interruptive clinical decision support (CDS) alerts within the electronic health record is essential to guide clinicians on the application of pharmacogenomic results at point of care. St. Jude Children's Research Hospital implemented a preemptive pharmacogenomic testing program in 2011 in a multidisciplinary effort involving extensive education to clinicians about pharmacogenomic implications. We conducted a retrospective analysis of clinicians' adherence to 4783 pharmacogenomically guided CDS alerts that triggered for 12 genes and 60 drugs. Clinicians adhered to the therapeutic recommendations provided in 4392 alerts (92%). In our population of pediatric patients with catastrophic illnesses, the most frequently presented gene/drug CDS alerts were TPMT/NUDT15 and thiopurines (n = 3850), CYP2D6 and ondansetron (n = 667), CYP2D6 and oxycodone (n = 99), G6PD and G6PD high-risk medications (n = 51), and CYP2C19 and proton pump inhibitors (omeprazole and pantoprazole; n = 50). The high adherence rate was facilitated by our team approach to prescribing and our collaborative CDS design and delivery.
Topics: Humans; Child; Decision Support Systems, Clinical; Pharmacogenetics; Cytochrome P-450 CYP2D6; Retrospective Studies; Electronic Health Records
PubMed: 36228116
DOI: 10.1093/jamia/ocac187 -
Journal of Medical Case Reports Mar 2022Coronavirus disease 2019 has been associated with adverse pregnancy outcomes, including preeclampsia. Coronavirus disease 2019 and preeclampsia have overlapping clinical...
BACKGROUND
Coronavirus disease 2019 has been associated with adverse pregnancy outcomes, including preeclampsia. Coronavirus disease 2019 and preeclampsia have overlapping clinical features and are therefore challenging to differentiate. Since pregnant women are not routinely tested for coronavirus disease 2019, it is prudent to test for it among patients presenting with preeclampsia or eclampsia.
CASE PRESENTATION
A 23-year-old female, a Munda, gravida 1 para 0, at 36 weeks and 5 days of amenorrhea presented to Mal Super Specialty Hospital as a referral in a semiconscious state after a severe attack of tonic-clonic seizures. Detailed history from the husband was insignificant except for a persistent cough for the last 7 days. She had denied any visual changes, headaches, or vaginal discharge. Physical examination revealed tachycardia (150 beats per minute), elevated blood pressure (187/111 mmHg), tachypnea (36 breaths per minute), and oxygen saturation of 94% on room air. Routine coronavirus disease 2019 rapid test was positive, and urine dipstick was +3. Additional tests revealed leukocytosis and elevated liver enzymes. Chest radiograph revealed prominent interstitial markings, and a bedside transabdominal ultrasonography showed a live single intrauterine fetus in cephalic presentation with normal cardiac activity and movements. A diagnosis of a prime gravida with eclampsia and coronavirus disease 2019 was made. She was managed with intravenous labetalol; she had already received a loading dose of intravenous magnesium sulfate, and we administered two maintenance doses during monitoring. Within an hour of admission, she had a spontaneous rupture of the amniotic membranes, with meconium-stained liquor (grade 2), and the fetal heart rate (148 beats per minute) was reassuring. She had an uncomplicated vaginal delivery of a live male newborn. Shortly after delivery, she developed slight respiratory distress and significant fluid overload that was managed with furosemide. Coronavirus disease 2019 reverse-transcription polymerase chain reaction test came back negative for the neonate and positive for the mother. She was shifted to the coronavirus disease 2019 treatment unit, and her contact with the child was limited. She was kept on a course of tablets ivermectin, zinc, vitamin C, montelukast, azithromycin, metronidazole, and injectable pantoprazole. The mother and child were discharged on day 15 after recovery with negative COVID nasopharyngeal swab.
CONCLUSION
A diagnosis of preeclampsia or eclampsia should prompt testing for coronavirus disease 2019.
Topics: Adult; COVID-19; Child; Eclampsia; Female; Hospitalization; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Complications; SARS-CoV-2; Young Adult
PubMed: 35232458
DOI: 10.1186/s13256-022-03308-8 -
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 -
Revista Espanola de Enfermedades... Mar 2023A 53-year-old lady with dysfunctional renal transplant and post-surgical hypoparathyroidism with phosphocalcic metabolism impairment was admitted to hospital because of...
A 53-year-old lady with dysfunctional renal transplant and post-surgical hypoparathyroidism with phosphocalcic metabolism impairment was admitted to hospital because of long-lasting epigastric pain and nausea. An esophagogastroduodenoscopy was performed, visualising a nodular lesion of 1 cm diameter with a depressed and ulcerated base. Microscopically the lesion was in relation with a metastatic calcinosis ulcer. Pantoprazole was initiated and serum phosphocalcic levels adjusted, achieving symptom remission. In the follow-up esophagogastroduodenoscopy, the lesion was healing with a fibrinous base and the histopathological report diagnosed superficial gastritis.
PubMed: 36896929
DOI: 10.17235/reed.2023.9495/2023 -
Terapevticheskii Arkhiv Oct 2022To evaluate the advantages of using combined therapy of proton-pump inhibitors (PPIs) and esophagoprotector in comparison with basic therapy of PPIs for 4 weeks based on...
AIM
To evaluate the advantages of using combined therapy of proton-pump inhibitors (PPIs) and esophagoprotector in comparison with basic therapy of PPIs for 4 weeks based on the results of changes in the endoscopic picture.To compare the effectiveness of 4-week PPI therapy and 4-week combination therapy with PPI and esophagoprotector Alfasoxx (sodium hyaluronate, chondroitin sulfate, poloxomer 407) in patients with erosive esophagitis (EE) of any degree according to the Los Angeles Endoscopic Classification.
MATERIALS AND METHODS
81 patients with EE AC according to the Los Angeles endoscopic classification (1994) was enrolled in the study on the basis of the clinic of Peter the Great, Mechnikov North-Western State Medical University. By computer randomization, patients were divided into the control group 40 patients (pantoprazole 40 mg 1 time per day) and the intervention group 41 patients (pantoprazole 40 mg 1 time per day + Alfasoxx 1 sachet qid). The therapy was carried out for 4 weeks. In all patients before and after therapy, the frequency and severity of the main symptoms of gastroesophageal reflux disease (GERD) were assessed, esophagogastroduodenoscopy was performed.
RESULTS
The advantage of combination therapy over standard PPI monotherapy in patients with EE was revealed. According to the results of the control endoscopy, healing of erosions of the esophageal mucosa was observed in 39 out of 41 (95.1%) patients in the intervention group and 32 out of 39 (82.1%) in the control group. The proportion of patients who showed an improvement in the endoscopic picture before and after treatment for 4 weeks by at least 1 level according to the Los Angeles classification was significantly higher in the comparison group 41 patients (100%), while in the control group 33 patients (85%); p0.009. After treatment, the combination therapy group had a lower incidence (p0.01) and severity of heartburn (p0.01). The same results are demonstrated by combination therapy regarding the symptom belching of air: in the study group after treatment, this symptom occurred less frequently (p=0.014), its severity was significantly less than in the control group (p0.01). There was a statistically significant decrease in the need for on-demand antacid therapy in the study group.
CONCLUSION
In this study involving 81 patients with erosive GERD, the benefits of combination therapy were demonstrated. The addition of Alfasoxx medical device to PPI therapy increases the clinical and endoscopic efficacy of therapy. This positive effect is associated with the esophagoprotective properties of the drug, based on unique pharmacodynamic characteristics. Combination therapy for GERD is preferred in patients with EE. Studies have shown the expediency of using Alfasoxx in case of insufficient effectiveness of classical acid-suppressive therapy for GERD.
Topics: Humans; Proton Pump Inhibitors; Pantoprazole; Antacids; Hyaluronic Acid; Chondroitin Sulfates; Esophagitis; Gastroesophageal Reflux; Peptic Ulcer; Treatment Outcome
PubMed: 36286979
DOI: 10.26442/00403660.2022.08.201828 -
Clinical Surgery Journal 2022Cannabinoid Hyperemesis Syndrome (CHS) is a form of cyclic vomiting syndrome characterized by episodic vomiting occurring every few weeks or months and is associated...
BACKGROUND
Cannabinoid Hyperemesis Syndrome (CHS) is a form of cyclic vomiting syndrome characterized by episodic vomiting occurring every few weeks or months and is associated with prolonged and frequent use of high-dose cannabis. CHS in the pediatric population has been increasingly reported over the last decade and can lead to life-threatening complications such as pneumomediastinum, which warrant careful consideration for surgical intervention.
CASE PRESENTATION
A 17-year-old female with no significant past medical history presented to the emergency department with abdominal pain, nausea, and vomiting for 24 hours. She had four episodes of green-yellow emesis followed by dry heaves. She also complained of chest and back pain, worse with deep inspiration. Upon further history, the patient reported a similar episode of abdominal pain and repetitive vomiting six months prior to the current episode. She smoked cannabis at least once daily and has done so for the past two years. Chest X-ray revealed a subtle abnormal lucency along the anteroposterior window and anterior mediastinum, consistent with a small amount of pneumomediastinum without any other acute intrathoracic abnormalities. Follow-up chest computed tomography with contrast showed multiple foci of air within the anterior and posterior mediastinum tracking up to the thoracic inlet. There was no evidence of contrast extravasation; however, small esophageal perforation could not be excluded. Given uncomplicated pneumomediastinum without frank contrast extravasation, the patient was treated medically with piperacillin-tazobactam, metronidazole, and micafungin for microbial prophylaxis; hydromorphone for pain control; as well as with pantoprazole, ondansetron, and promethazine. Nutrition was provided via total parenteral nutrition. The patient was intensely monitored for signs of occult esophageal perforation, but none were detected. She was advanced to a soft diet on hospital day eight, solid food diet on day nine, at which point antibiotics were discontinued, and the patient was subsequently discharged.
CONCLUSION
CHS in an increasingly common disorder encountered in the pediatric setting due to rising prevalence of cannabis use. The management of CHS and potentially life-threatening complications such as pneumomediastinum should be given careful consideration. Pneumomediastinum can be a harbinger of more sinister pathology such as esophageal perforation, which may warrant urgent surgical intervention.
PubMed: 36438163
DOI: No ID Found