Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study

2020 ◽  
Vol 21 (2) ◽  
pp. 126-131
Author(s):  
Bhuvanachandra Pasupuleti ◽  
Vamshikrishna Gone ◽  
Ravali Baddam ◽  
Raj Kumar Venisetty ◽  
Om Prakash Prasad

Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

2021 ◽  
pp. 20200505
Author(s):  
Aykağan Coşgunarslan ◽  
Emin Murat Canger ◽  
Damla Soydan Çabuk

Objectives: Proton pump inhibitors (PPI) provide a long-lasting anti-acidic effect by inhibiting the proton pump, and they are one of the most commonly prescribed drugs worldwide. PPIs adversely affect the bone structure via deficiency of vitamins and minerals. The aim of this study was to investigate the possible PPI-induced bone changes in the mandible on panoramic radiographs with the methods of fractal analysis and panoramic morphometric indices. Methods: Panoramic radiographs of 402 patients were used (201 PPI users, 201 control group). Fractal analysis was performed on 4 regions of interests (ROI): 1- upper part of the ramus, 2- angulus, 3- anterior of the mental foramen, 4- distal of the middle ramus. Also, the panoramic mandibular index (PMI), mandibular cortical width (MCW), and Klemetti index (KI) were performed on radiographs. Results: There were significant differences in terms of ROI3, MCW, and KI between the control and study groups (p < 0.05) while there was no significant difference for ROI1, ROI2, ROI4, and PMI (p > 0.05). Males were severely affected than females. Conclusions: Osteoporotic changes were detected in the trabecular and cortical bone in the mental foramen region in PPI users with fractal analysis and morphometric indices, while there were no differences for mandibular ramus and angulus regions according to fractal analysis.


2020 ◽  
Vol 129 (8) ◽  
pp. 781-787
Author(s):  
Minsuk Chae ◽  
Dong Hyuk Jang ◽  
Ho Chan Kim ◽  
Minsu Kwon

Objectives: To identify whether combination therapy with mucolytics and proton pump inhibitors (PPIs) leads to faster and more effective symptomatic relief in patients with laryngopharyngeal reflux (LPR). Methods: Patients diagnosed as LPR with a reflux symptom index (RSI) ≥ 13 and a reflux finding score (RFS) ≥ 7 were enrolled in this prospective study. Patients were randomly allocated to control (PPI only) or experimental (PPI + mucolytics) groups and changes in RSI and RFS values were assessed at 1- and 3-month follow-up. Results: One hundred sixteen patients were randomly allocated into either the control group ( n = 59) or the experimental group ( n = 57). The RSI and RFS scores significantly decreased in both groups (all P < .001) after 1 month of treatment; however, there was no significant difference in RSI change between groups ( P = .223). After 3 months of treatment, there remained no significant difference in RSI change between groups ( P = .592). Conclusions: Combination therapy with mucolytics and PPI compared to PPI alone did not lead to faster or more effective symptomatic relief in LPR patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shengyu Zhang ◽  
Ziying Han ◽  
Yuelun Zhang ◽  
Xiaomao Gao ◽  
Shicheng Zheng ◽  
...  

Background: Acute pancreatitis (AP) is a systemic inflammatory disorder with a wide spectrum of clinical symptoms that can range from mild to severe. Previous preclinical study results suggest that proton pump inhibitors (PPIs) can inhibit exocrine pancreatic secretion and exert anti-inflammatory properties, which might in turn improve the outcome of AP.Aim: We conducted this multicenter, retrospective cohort study to investigate the potential effects of PPIs on the mortality, and total duration of hospital stay and local complication occurrence of patients with AP.Methods: A total of 858 patients with AP were included. All patients presented to the hospital within 48 h of symptom onset and were divided into the following two groups: patients who were treated with PPIs (n = 684) and those not treated with PPIs (n = 174). We used propensity score matching (PSM) analysis to reduce confounding bias before comparing the outcomes between the two groups.Results: Before PSM analysis, there were significant differences in a number of parameters between the two groups, including age, sex, hematocrit, blood urea nitrogen, peritonitis signs, Ranson’s score, and Acute Physiology Chronic Health Evaluation II score and organ failure occurrence. Before PSM, the PPIs group had a higher rate of mortality than the control group [RR = 1.065; 95% confidence ratio (CI) 1.045–1.086; p = 0.001]. After PSM, there was no significant difference in mortality (RR = 1.009; 95% CI, 0.999–1.019; p = 0.554) or total hospital stay (p = 0.856), although the PPIs group had a lower occurrence of pancreatic pseudocyst (RR = 0.416; 95% CI 0.221–0.780; p = 0.005).Conclusion: This study showed that PPIs therapy was not associated with reduced mortality or total hospital stay, but was associated with a reduction in the occurrence of pseudocysts in patients with acute pancreatitis.


Author(s):  
Xiao-Yu Zhang ◽  
Hai-Bing Wu ◽  
Yun Ling ◽  
Zhi-Ping Qian ◽  
Liang Chen

ABSTRACTBackground/aimsTo evaluate the effect of proton pump inhibitors on the course of common COVID-19.MethodsClinical data of common COVID-19 patients admitted to the Shanghai public health clinical center for treatment from January 20, 2020 to March 16, 2020 were collected. A retrospective study was conducted and the patients were divided into two groups according to whether they used proton pump inhibitors or not. The differences in SARS-CoV-2 clearance and hospital stay between the two groups were compared by univariate and multivariate analyses.ResultsA total of 154 COVID-19 common cases were included in this study, including 80 males (51.9%), 35 patients (22.7%) in the proton pump inhibitors group, and 119 patients (77.3%) in the control group. In the proton pump inhibitors group and the control group, the duration of SARS-CoV-2 clearance were 7(6-9) and 7(6-11) days, and the duration of hospital stay was 21(16-25) and 20(15-26) days, respectively. There was no significant difference between the two groups in the cumulative incidence of SARS-CoV-2 clearance and the cumulative incidence of discharge, and the same after Propensity Score Match, all P > 0.05. Multivariate analysis suggested that chronic gastropathy prolonged the duration of SARS-CoV-2 clearance, the HR was 20.924(3.547-123.447). Hypertension, chronic obstructive pulmonary disease, chronic liver disease and malignant tumor all increased the duration of hospital stay for COVID-19, and the HR were 1.820 (1.073-3.085), 4.370 (1.205-15.844), 9.011 (2.681-30.290) and 5.270 (1.237-22.456), respectively; the duration of hospital stay in COVID-19 patients was shortened by SARS-CoV-2 clearance, and the HR was 0.907 (0.869-0.947); all P < 0.05.ConclusionProton pump inhibitors use have no effect on the prolonging or shortening of the course of adults hospitalized with COVID-19.


2020 ◽  
Author(s):  
xiaoyu ZHANG ◽  
Haibing Wu ◽  
Yun Ling ◽  
Liang Chen

Abstract Background/aims: This study is to evaluate the effect of proton pump inhibitors on the course of common COVID-19.Methods: Clinical data of common COVID-19 patients admitted to the Shanghai Public Health Clinical Center for treatment from January 20, 2020 to March 16, 2020 were collected. A retrospective study was conducted and the patients were divided into two groups according to whether they used proton pump inhibitors or not. The differences in SARS-CoV-2 clearance and hospital stay between the two groups were compared by univariate and multivariate analyses.Results: A total of 154 COVID-19 common cases were included in this study, including 80 males (51.9%), 35 patients (22.7%) in the proton pump inhibitors group, and 119 patients (77.3%) in the control group. In the proton pump inhibitors group and the control group, the duration of the SARS-CoV-2 clearance were 7(6-9) and 7(6-11) days, and the duration of the hospital stay was 21(16-25) and 20(15-26) days, respectively. There was no significant difference between the two groups in the cumulative incidence of the SARS-CoV-2 clearance and the discharge, all P > 0.05. Multivariate analysis showed that chronic gastropathy prolonged the duration of SARS-CoV-2 clearance, the HR was 20.924(3.547-123.447). Hypertension, chronic obstructive pulmonary disease, chronic liver disease and malignant tumor all increased the duration of hospital stay for COVID-19, and the HR were 1.820 (1.073-3.085), 4.370 (1.205-15.844), 9.011 (2.681-30.290) and 5.270 (1.237-22.456), respectively; the duration of the hospital stay in COVID-19 patients was shortened by the SARS-CoV-2 clearance, and the HR was 0.907 (0.869-0.947); all P < 0.05.Conclusion: Proton pump inhibitors use has no effect on the prolonging or shortening of the course of adults hospitalized with COVID-19.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ádám László Nagy ◽  
Zsolt Tóth ◽  
Tamás Tarjányi ◽  
Nándor Tamás Práger ◽  
Zoltán Lajos Baráth

Abstract Background In this research the biomechanical properties of a bone model was examined. Porcine ribs are used as experimental model. The objective of this research was to investigate and compare the biomechanical properties of the bone model before and after implant placement. Methods The bone samples were divided in three groups, Group 1 where ALL-ON-FOUR protocol was used during pre-drilling and placing the implants, Group 2 where ALL-ON-FOUR protocol was used during pre-drilling, and implants were not placed, and Group 3 consisting of intact bones served as a control group. Static and dynamic loading was applied for examining the model samples. Kruskal–Wallis statistical test and as a post-hoc test Mann–Whitney U test was performed to analyze experimental results. Results According to the results of the static loading, there was no significant difference between the implanted and original ribs, however, the toughness values of the bones decreased largely on account of predrilling the bones. The analysis of dynamic fatigue measurements by Kruskal–Wallis test showed significant differences between the intact and predrilled bones. Conclusion The pre-drilled bone was much weaker in both static and dynamic tests than the natural or implanted specimens. According to the results of the dynamic tests and after a certain loading cycle the implanted samples behaved the same way as the control samples, which suggests that implantation have stabilized the skeletal bone structure.


2015 ◽  
Vol 52 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Sílvia Maria Perrone CAMILO ◽  
Élia Cláudia de Souza ALMEIDA ◽  
Benito André Silveira MIRANZI ◽  
Juliano Carvalho SILVA ◽  
Rosemary Simões NOMELINI ◽  
...  

Background Proton-pump inhibitors have been used for at least two decades. They are among the most commonly sold drugs in the world. However, some controversy remains about the indications for their use and the consequences of their prolonged use. Objectives To evaluate and compare the endoscopic and histopathologic gastric changes in chronic users of proton-pump inhibitors to changes in non-users. Methods A prospective study performed at a tertiary Public Hospital involving 105 patients undergoing upper-gastrointestinal endoscopy. Subjects included 81 proton-pump inhibitor users and 24 non-users (control group). Biopsies of the antral-type mucosa, the antral-fundic transition, and the fundus were evaluated by the Sydney System. The presence of erosion or ulceration, lymphatic follicles, reactive gastropathy, and polypoid or epithelial hyperplasia was also determined. Serum levels of gastrin were measured. Results We found two polyps, one in each group, both of which were negative for Helicobacter pylori. There were two cases of parietal cell hyperplasia in users of proton-pump inhibitors. Gastrin was elevated in 28 users of proton-pump inhibitors and in four members of the control group. We did not find statistically significant differences in the endoscopic or histopathologic findings between the two groups. Conclusions Chronic use of proton-pump inhibitors for the duration examined was not associated with significant gastric changes. An interesting finding was that the 4 chronic users of proton-pump inhibitors who had serum gastrin levels above 500 pg/mL also had positive serology for Chagas disease.


1984 ◽  
Vol 62 (12) ◽  
pp. 1479-1486 ◽  
Author(s):  
Jean-Paul Clozel ◽  
Jacques Billette ◽  
Gilles Caillé ◽  
Pierre Théroux ◽  
Richard Cartier

Atrial and atrioventricular conduction variables were studied at control and at the end of each of six consecutive 45-min diltiazem administration periods in eight closed chest-anesthetized dogs. Diltiazem was given as a bolus (50 μg/kg, i.v.) followed by an infusion (0.5 μg∙kg−1∙min−1); doses were doubled in subsequent periods. The plasma concentrations, measured by gas–liquid chromatography, ranged from 8 to 1400 ng/mL and correlated strongly with the doses (r = 0.92; p < 0.01). The Wenckebach cycle length, basic conduction time, and functional refractory period of the atrioventricular (AV) node increased proportionally with plasma concentration (respective r = 0.90, 0.89, 0.80; p < 0.01). The minimum mean plasma concentrations affecting these variables significantly were 37, 83, and 175 ng/mL, respectively. Second or third degree AV blocks developed in all dogs for plasma concentrations between 379 and 1400 ng/mL. In four dogs which were given isoproterenol (0.2 μg∙kg−1∙min−1), these blocks disappeared within 1 min. Atrial conduction time and functional refractory period were slightly but significantly shortened by diltiazem with mean plasma concentrations of 175 ng/mL and over. His–Purkinje intervals were not significantly changed by diltiazem. Systolic and diastolic arterial pressures were decreased by diltiazem (r = −0.64, r = −0.79; p < 0.01) starting with a mean plasma concentration of 83 ng/mL. We conclude that AV nodal conduction variables are progressively prolonged with increasing plasma concentrations of diltiazem; plasma concentrations affecting blood pressure and AV nodal variables overlap; and the AV blocks produced by toxic concentrations of diltiazem can be corrected by isoproterenol.


2018 ◽  
Vol 47 ◽  
pp. 07006
Author(s):  
Saryono Saryono ◽  
Hesti Devinta ◽  
Abdul Haris Budi Widodo ◽  
Arif Imam Hidayat

Contaminated water often affects the occurrence of periodontitis in the coastal area. The diabetic hypercholesterolemia-induced periodontitis in Indonesia is very high. The use of coenzyme Q10 to treat this disease has never been investigated yet. Therefore, this study aimedto analyze the effect of coenzyme Q10 on the lipid profile of diabetic hypercholesterolemia-induced periodontitis.Twenty four rats were randomized into 6 groups (G1-G6). The groups (G1-G3) are healthy, negative and positive control group respectively. The treatment groups (G4-G6) are diabetic hypercholesterolemia-induced rats given coenzyme q10 dose of 13,5; 27 and 54 mg/kg respectively. Rats were induced by periodontitis, hypercholesterolemia and diabetes mellitus. Coenzyme Q10 was administered orally using 2 mL gastric tube once a day for 14 days. Lipid profile including triglycerides, HDL, and atherogenic index (IA) was measured enzymatically by the CHOD-PAP method. Data were analyzed by one-way ANOVA test and followed by the Least Significant Difference (LSD) post hoc test.Coenzyme Q10 with a dose of 54 mg/kgis effective in lowering triglyceride, and atherogenic index and increasing HDL level in diabetic hyperlipidemia-induced periodontitis rats model. This research supports the potential effects of coenzyme Q10 supplementation to improve lipid profile in diabetic hypercholesterolemia-induced periodontitis in the coastal area.


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