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Therapeutic Advances in Gastroenterology Nov 2016The pharmacokinetics and pharmacodynamics of a novel orally disintegrating tablet (ODT) formulation of delayed-release dexlansoprazole 30 mg was evaluated the...
BACKGROUND
The pharmacokinetics and pharmacodynamics of a novel orally disintegrating tablet (ODT) formulation of delayed-release dexlansoprazole 30 mg was evaluated the dexlansoprazole 30 mg capsule in this phase I, open-label, multiple-dose, randomized, two-period crossover study.
METHODS
Healthy adults received daily doses of 30 mg dexlansoprazole ODT or 30 mg dexlansoprazole delayed-release capsule for 5 days during two treatment periods, separated by a 7-day washout interval. Blood samples for dexlansoprazole plasma concentrations and intragastric pH measurements were collected through 24 hours postdose on days 1 and 5 of each period.
RESULTS
Bioequivalence between the 30 mg ODT and 30 mg capsule dosage forms was demonstrated by the primary endpoints of dexlansoprazole peak concentration () and systemic exposure (AUC) values contained within the prespecified 90% confidence interval (CI) range of 0.80-1.25. Additional primary endpoints of intragastric mean pH values and percentage of time with pH > 4 over the 24-hour postdose interval were equivalent for dexlansoprazole ODT and dexlansoprazole capsule. Treatment-emergent adverse events were reported in 23% and 28% of participants receiving the ODT and capsule formulations, respectively. Headache was the most common adverse event in both treatment regimens (5.8% with ODT and 6.0% with capsule).
CONCLUSIONS
Administration of dexlansoprazole 30 mg ODT or 30 mg capsule provided equivalent plasma exposure when either was administered as a single dose or as once daily doses for 5 days. Pharmacodynamic equivalence between the two formulations was demonstrated by similar intragastric pH parameters on both day 1 and day 5. No effect of day on dexlansoprazole pharmacokinetics was observed. Dexlansoprazole ODT and dexlansoprazole capsule were both well tolerated.
PubMed: 27803731
DOI: 10.1177/1756283X16670073 -
Therapeutics and Clinical Risk... 2015The management of gastroesophageal reflux disease (GERD) has been revolutionized with the development of proton pump inhibitors (PPIs). Unfortunately, due to the... (Review)
Review
The management of gastroesophageal reflux disease (GERD) has been revolutionized with the development of proton pump inhibitors (PPIs). Unfortunately, due to the inherent pharmacokinetic and pharmacodynamic profiles of conventional PPIs, many patients continue to suffer from symptoms related to GERD despite appropriate use of PPIs. Dexlansoprazole MR is a PPI with a unique dual delayed-release delivery system that has been designed to address the unmet needs in GERD management. Specifically, dexlansoprazole MR addresses limitations with short plasma half-life and need for meal-associated dosing, characteristic of conventional PPIs. In addition, dexlansoprazole MR has been shown to be effective in several specific clinical situations. These include coadministration with clopidogrel, healing of all grades of erosive esophagitis, improvement in reflux-related quality of life, step down to once-per-day dosing, and treatment of Helicobacter pylori infections. Furthermore, dexlansoprazole MR has been found to induce symptom improvement in patients with nonerosive esophageal reflux disease, nocturnal heartburn and GERD-related sleep disturbance, and regurgitation. Overall, dexlansoprazole MR is a unique and useful tool in the management of GERD.
PubMed: 26586949
DOI: 10.2147/TCRM.S66680 -
Clinical and Experimental... 2016Gastroesophageal reflux disease is the most common upper gastroenterology disorder in the US. It is associated with a variety of complications and significantly impacts... (Review)
Review
Gastroesophageal reflux disease is the most common upper gastroenterology disorder in the US. It is associated with a variety of complications and significantly impacts quality of life. Proton pump inhibitors are the most effective treatment. Dexlansoprazole modified release (MR) is a proton pump inhibitor that employs a novel release formulation that prolongs its absorption and allows for more flexibility in dosing. Dexlansoprazole MR can be dosed without regard to food intake or time of day, and once-daily dosing may replace twice-daily dosing of other agents. Dexlansoprazole MR is effective for healing and maintenance of erosive esophagitis, and for the treatment of nonerosive disease, including nocturnal gastroesophageal reflux disease. Dexlansoprazole MR is safe and well tolerated, and can improve quality of life.
PubMed: 27471402
DOI: 10.2147/CEG.S91602 -
Gut and Liver Jan 2023Tegoprazan, a novel potassium-competitive acid blocker, is expected to overcome the limitations of proton pump inhibitors and effectively control nocturnal acid... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/AIMS
Tegoprazan, a novel potassium-competitive acid blocker, is expected to overcome the limitations of proton pump inhibitors and effectively control nocturnal acid breakthrough. To evaluate the pharmacodynamics of tegoprazan versus dexlansoprazole regarding nocturnal acid breakthrough in healthy subjects.
METHODS
In a randomized, open-label, single-dose, balanced incomplete block crossover study, 24 healthy male volunteers were enrolled and randomized to receive oral tegoprazan (50, 100, or 200 mg) or dexlansoprazole (60 mg) during each of two administration periods, separated by a 7- to 10-day washout period. Blood samples were collected for pharmacokinetic parameter analysis; gastric monitoring was performed for pharmacodynamic parameter evaluation.
RESULTS
All 24 subjects completed the study. Average maximum plasma concentration, area under the plasma concentration-time curve, and mean time with gastric pH >4 and pH >6 for tegoprazan demonstrated dose-dependent incremental increases. All the tegoprazan groups reached mean pH ≥4 within 2 hours, whereas the dexlansoprazole group required 7 hours after drug administration. Based on pharmacodynamic parameters up to 12 hours after evening dosing, 50, 100, and 200 mg of tegoprazan presented a stronger acid-suppressive effect than 60 mg of dexlansoprazole. Moreover, the dexlansoprazole group presented a comparable acid-suppressive effect with the tegoprazan groups 12 hours after dosing.
CONCLUSIONS
All the tegoprazan groups demonstrated a significantly faster onset of gastric pH increase and longer holding times above pH >4 and pH >6 up to 12 hours after evening dosing than the dexlansoprazole group.
Topics: Humans; Male; Dexlansoprazole; Cross-Over Studies; Proton Pump Inhibitors; Benzene Derivatives
PubMed: 36317518
DOI: 10.5009/gnl220050 -
Clinical and Experimental... 2014To evaluate the safety and pharmacokinetic profile of dexlansoprazole modified-release (MR) capsules in pediatric patients with symptomatic gastroesophageal reflux...
OBJECTIVE
To evaluate the safety and pharmacokinetic profile of dexlansoprazole modified-release (MR) capsules in pediatric patients with symptomatic gastroesophageal reflux disease (GERD).
METHODS
This Phase I, open-label study enrolled male and female patients (1 to 11 years of age) with GERD. Patients received dexlansoprazole MR 15 mg, 30 mg, or 60 mg (according to weight) once daily for 7 days. Blood samples for the measurement of plasma dexlansoprazole concentrations were collected for 24 hours after the day 7 dose. Dexlansoprazole plasma concentrations and pharmacokinetic parameters were summarized by dose group. Safety assessments included adverse events (AEs), clinical laboratory evaluations, fasting gastrin concentrations, physical examinations, electrocardiograms, and vital signs.
RESULTS
Thirty-six patients received study drug (12 per dose group), and 31 had evaluable pharmacokinetic data. There was a significant effect of weight on dose-normalized area under the curve (AUC, P=0.003) and dose-normalized maximum plasma concentration (Cmax) (P=0.013), indicating that for a given dose, dexlansoprazole exposure decreases as body weight increases. After adjusting for body weight, both dexlansoprazole Cmax and AUC increased in an approximately dose-proportional manner with increasing dexlansoprazole dose. A total of ten of 36 patients reported at least one treatment-emergent AE, with most events considered mild in intensity. The most common AEs were vomiting, abdominal pain, diarrhea, and nausea.
CONCLUSION
In 1- to 11-year-old patients with symptomatic GERD, weight-adjusted dexlansoprazole AUC and Cmax increased approximately dose-proportionally. However, for a given dose, dexlansoprazole exposure decreased with increasing body weight. Dexlansoprazole MR was well tolerated, and the incidence of AEs did not increase with increasing dose.
PubMed: 25525378
DOI: 10.2147/CEG.S67672 -
Clinical Drug Investigation Oct 2019This study was performed in healthy Chinese subjects to evaluate the safety and pharmacokinetic/pharmacodynamic characteristics of a novel injection formulation of... (Clinical Trial)
Clinical Trial Comparative Study
BACKGROUND AND OBJECTIVE
This study was performed in healthy Chinese subjects to evaluate the safety and pharmacokinetic/pharmacodynamic characteristics of a novel injection formulation of dexlansoprazole in the context of single and multiple administration, compared with the original lansoprazole injection.
METHODS
Helicobacter pylori-negative healthy volunteers were recruited, and 70 participants were enrolled into five dosing groups (seven males and seven females in each group), including 15 mg once daily (qd), 15 mg every 12 h (q12h), 30 mg qd and 30 mg q12h of dexlansoprazole treatment for 5 days, as well as 30 mg q12h of lansoprazole treatment for 5 days. Blood samples were collected at scheduled time spots postdose on day 1 (first dose) and day 5 (last dose). Twenty-four-hour intragastric pH was continuously monitored on day 0 (baseline) and days 1 and 5. Dexlansoprazole and S-lansoprazole in human plasma were determined by validated chiral liquid chromatography with tandem mass spectrometry, and the pharmacokinetic parameters were determined by a non-compartmental method using Phoenix WinNonlin software. Safety assessment included changes in vital signs and laboratory tests, physical examination findings, and incidence or reports of adverse events.
RESULTS
The half-life (t) and clearance (CL) of dexlansoprazole were 1.76-2.06 h and 4.52-5.40 L/h, respectively, while the t and CL of S-lansoprazole were 0.87-1.02 h and 34.66-35.98 L/h, respectively. No drug accumulation after repeated administration was noted. Administration of lansoprazole 30 mg resulted in higher area under the concentration-time curve from time zero to the last measurable concentration (AUC) of dexlansoprazole than that of dexlansoprazole 15 mg (p = 0.026). Zero to 24 h after q12h multiple dosing, median and mean intragastric pH, percentage of time with the intragastric pH above 4.0 [TpH ≥ 4.0(%)] and percentage of time with the intragastric pH above 6.0 [TpH ≥ 6.0(%)] in the dexlansoprazole 15 mg q12h group were 6.07 ± 0.61, 5.70 ± 0.76, 83.58 ± 12.34, and 53.70 ± 17.06, respectively, which was similar to the lansoprazole 30 mg q12h group, i.e. 6.15 ± 0.62, 5.88 ± 0.67, 87.26 ± 12.08 and 57.00 ± 16.35, respectively. A weak positive correlation between dexlansoprazole AUC and baseline-adjusted TpH ≥ 4.0(%) over 0-24 h was observed, with Pearson correlation coefficients of 0.437 (p = 0.029), while no correlation was observed between AUC and baseline-adjusted TpH ≥ 6.0(%) over 0-24 h.
CONCLUSION
Every 12 h intravenous dosing of dexlansoprazole up to 30 mg for 5 days was safe and well-tolerated in healthy Chinese subjects. Every 12 h dosing of dexlansoprazole 15 mg has a comparable effect of gastric acid inhibition as lansoprazole 30 mg q12h.
TRIAL REGISTRATION
ClinicalTrials.gov ID NCT03120273.
Topics: Adult; China; Chromatography, Liquid; Dexlansoprazole; Dose-Response Relationship, Drug; Female; Healthy Volunteers; Humans; Infusions, Intravenous; Lansoprazole; Male; Proton Pump Inhibitors; Tandem Mass Spectrometry; Young Adult
PubMed: 31338800
DOI: 10.1007/s40261-019-00824-2 -
Digestive Diseases and Sciences Feb 2019In gastroesophageal reflux disease (GERD), the frequency of heartburn symptoms and erosive esophagitis (EE) increases with age in children and adolescents. Proton pump... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In gastroesophageal reflux disease (GERD), the frequency of heartburn symptoms and erosive esophagitis (EE) increases with age in children and adolescents. Proton pump inhibitor, dexlansoprazole, is approved for healing EE of all grades, maintenance of healed EE, relief of heartburn, and treatment of symptomatic non-erosive GERD in patients ≥ 12 years.
AIM
To assess safety and efficacy of dexlansoprazole dual delayed-release capsule in healing of EE and maintenance of healed EE in adolescents.
METHODS
A multicenter, phase 2, 36-week study was conducted in 62 adolescents (12-17 years) with endoscopically confirmed EE. Patients received dexlansoprazole 60 mg once daily (QD) during open-label healing phase. Those with confirmed healing at week 8 were randomized to dexlansoprazole 30 mg QD or placebo during 16-week, double-blind maintenance phase, with subsequent treatment-free follow-up of ≥ 12 weeks. Primary endpoints were treatment-emergent adverse events (TEAEs) in ≥ 5% of patients during treatment. Secondary endpoints included percentages of patients with healing of EE and with maintenance of healed EE.
RESULTS
88% of patients achieved EE healing, and 61.3% reported a TEAE [headache (12.9%), oropharyngeal pain (8.1%), diarrhea (6.5%), and nasopharyngitis (6.5%)]. During maintenance phase, healing was maintained in 82% and 58% of dexlansoprazole and placebo groups, respectively. 72.0% of dexlansoprazole-treated patients reported TEAEs, which included headache (24.0%), abdominal pain (12.0%), nasopharyngitis (12.0%), pharyngitis (12.0%), sinusitis (12.0%), bronchitis (8.0%), upper respiratory tract infection (8.0%), and insomnia (8.0%); 61.5% experienced a TEAE with placebo.
CONCLUSIONS
Dexlansoprazole is safe and efficacious for healing EE and maintenance of healed EE in adolescents.
Topics: Abdominal Pain; Adolescent; Child; Delayed-Action Preparations; Dexlansoprazole; Diarrhea; Double-Blind Method; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Headache; Humans; Maintenance Chemotherapy; Male; Nasopharyngitis; Oropharynx; Pain; Pharyngitis; Proton Pump Inhibitors; Sleep Initiation and Maintenance Disorders; Treatment Outcome
PubMed: 30390234
DOI: 10.1007/s10620-018-5325-8 -
Clinical and Experimental... 2009Although proton pump inhibitors (PPI) have a record of remarkable effectiveness and safety in the management of gastroesophageal reflux disease (GERD), several treatment...
Although proton pump inhibitors (PPI) have a record of remarkable effectiveness and safety in the management of gastroesophageal reflux disease (GERD), several treatment challenges with PPI have emerged. Dexlansoprazole MR is the (R)-enantiomer of lansoprazole contained in a formulation that produces two distinct releases of drug and significantly extends the duration of active plasma concentrations and % time pH > 4 beyond that of conventional single-release PPI. Dexlansoprazole MR can be administered without regard to meals or the timing of meals in most patients. Dexlansoprazole MR 60 mg demonstrated similar efficacy for healing of erosive esophagitis at 8 weeks compared with lansoprazole 30 mg, and dexlansoprazole MR 30 mg was superior to placebo for maintenance of healed erosive esophagitis at 6 months with 99% of nights and 96% of days heartburn-free over 6 months in patients taking dexlansoprazole MR 30 mg. Superior relief of heartburn occurred in patients taking dexlansoprazole MR 30 mg (55% heartburn-free 24-hour periods) vs placebo (14%) for symptomatic nonerosive GERD. The safety profile of dexlansoprazole MR is similar to that of lansoprazole. The extended pharmacodynamic effects, added convenience, and efficacy and safety of dexlansoprazole MR offer a novel approach to gastric pH control in patients with acid-related disorders.
PubMed: 21694835
DOI: 10.2147/ceg.s5765 -
The Korean Journal of Gastroenterology... Oct 2017Recently, the eradication rate of () infection has decreased to less than 80% worldwide with the use of clarithromycin-based triple therapy owing to the increased...
BACKGROUND/AIMS
Recently, the eradication rate of () infection has decreased to less than 80% worldwide with the use of clarithromycin-based triple therapy owing to the increased resistance of to antibiotics, especially clarithromycin and metronidazole. This prospective study aimed to determine eradication rate of following high and frequent doses of extended-release dexlansoprazole and amoxicillin, as a dual therapy in a region with high clarithromycin resistance rate.
METHODS
A total of 50 treatment-naïve patients with active infections, who were confirmed through via rapid urease test or histology and serology between November 2015 and February 2016 at our hospital, were included for analysis. All enrolled patients were treated with 750 mg amoxicillin and 30 mg dexlansoprazole, four times a day for a total duration of 14 days. Treatment success was determined using urea breath test four weeks after treatment completion.
RESULTS
Seven out of the 50 patients (29 men and 21 women; mean age, 57 years) dropped out during the study. The total eradication rate was 52% (26/50), and that for those with a compliance rate of over 90% was 68.4% (26/38). infections were not successfully eradicated in patients with a compliance rate of less than 90%. Nine patients (18%) reported side effects, such as mild diarrhea and abdominal fullness. No significant factors, such as smoking and alcohol consumption, affected the infection the eradication rate.
CONCLUSIONS
High and frequent doses of proton pump inhibitor-amoxicillin dual therapy were not effective in eradicating infection in a province with high clarithromycin resistance rate.
Topics: Amoxicillin; Anti-Bacterial Agents; Breath Tests; Dexlansoprazole; Diarrhea; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors
PubMed: 29060955
DOI: 10.4166/kjg.2017.70.4.176 -
Journal of Neurogastroenterology and... Jul 2016Although gastroesophageal reflux disease is not as common in Asia as in western countries, the prevalence has increased substantially during the past decade.... (Review)
Review
Pharmacological and Safety Profile of Dexlansoprazole: A New Proton Pump Inhibitor - Implications for Treatment of Gastroesophageal Reflux Disease in the Asia Pacific Region.
Although gastroesophageal reflux disease is not as common in Asia as in western countries, the prevalence has increased substantially during the past decade. Gastroesophageal reflux disease is associated with considerable reductions in subjective well-being and work productivity, as well as increased healthcare use. Proton pump inhibitors (PPIs) are currently the most effective treatment for gastroesophageal reflux disease. However, there are limitations associated with these drugs in terms of partial and non-response. Dexlansoprazole is the first PPI with a dual delayed release formulation designed to provide 2 separate releases of medication to extend the duration of effective plasma drug concentration. Dexlansoprazole has been shown to be effective for healing of erosive esophagitis, and to improve subjective well-being by controlling 24-hour symptoms. Dexlansoprazole has also been shown to achieve good plasma concentration regardless of administration with food, providing flexible dosing. Studies in healthy volunteers showed no clinically important effects on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition, with no dose adjustment of clopidogrel necessary when coprescribed. This review discusses the role of the new generation PPI, dexlansoprazole, in the treatment of gastroesophageal reflux disease in Asia.
PubMed: 26932927
DOI: 10.5056/jnm15150