Dexlansoprazole

Pharmaceuticals -> Alimentary tract and metabolism -> Drugs for acid related disorders

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Used in Switzerland

Breast Feeding; Lactation; Milk, Human; Anti-Ulcer Agents; Gastrointestinal Agents; Proton Pump Inhibitors

Breast Feeding; Lactation; Milk, Human; Anti-Ulcer Agents; Gastrointestinal Agents; Proton Pump Inhibitors

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Warning

H315 (33.3%): Causes skin irritation [Warning Skin corrosion/irritation]

P203, P260, P261, P264, P264+P265, P271, P272, P280, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P332+P317, P333+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 3 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Dexlansoprazole

vLess-DILI-concern

4

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

◉ Summary of Use during Lactation

◉ Summary of Use during Lactation

A - Alimentary tract and metabolism

QA - Alimentary tract and metabolism

Dexlansoprazole is a proton pump inhibitor (PPI) that suppresses both basal and stimulated gastric acid secretion. PPIs are associated with a risk for a rebound effect and a short-term increase in hypersecretion; thus, such risk cannot be excluded with dexlansoprazole. With long-term use, PPIs are also associated with a risk of increased susceptibility to bacterial infections, vitamin B12 and iron deficiency, and hypomagnesemia and hypocalcemia, possibly leading to osteoporosis and bone fractures. Dexlansoprazole is reported to interfere with the secretin stimulation test and create false positive urine screening tests for tetrahydrocannabinol. Dexlansoprazole can increase gastrin levels, which can cause enterochromaffin-like cell hyperplasia and increase serum CgA levels. Increased CgA levels may cause false positive results in diagnostic investigations for neuroendocrine tumours.

Dexlansoprazole suppresses gastric acid secretion by blocking the final step of acid production. It inhibits the H/K ATPase at the secretory surface of the gastric parietal cell, which is involved in the secretion of hydrochloric acid. H/K ATPase is a proton pump responsible for hydrolyzing ATP and exchanging H⁺ ions from the cytoplasm for K⁺ ions in the secretory canaliculus: this action results in hydrochloric acid secretion into the gastric lumen.

Dexlansoprazole is extensively metabolized in the liver. It undergoes oxidation and reduction, followed by subsequent sulfation, glucuronidation, and glutathione conjugation to form inactive metabolites. Oxidative metabolites are formed from CYP2C19-mediated hydroxylation and CYP3A4-mediated oxidation to the sulfone. CYP2C19 is a polymorphic liver enzyme which exhibits three phenotypes in the metabolism of CYP2C19 substrates: extensive metabolizers (*1/*1), intermediate metabolizers (*1/mutant) and poor metabolizers (mutant/mutant). Dexlansoprazole is the major circulating component in plasma regardless of CYP2C19 metabolizer status. In CYP2C19 intermediate and extensive metabolizers, the major plasma metabolites are 5-hydroxy dexlansoprazole and its glucuronide conjugate, while in CYP2C19 poor metabolizers dexlansoprazole sulfone is the major plasma metabolite.

Lansoprazole has known human metabolites that include 5-Hydroxylansoprazole and Lansoprazole Sulfone.

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DEXLANSOPRAZOLE

Established Pharmacologic Class [EPC] - Proton Pump Inhibitor

Mechanisms of Action [MoA] - Proton Pump Inhibitors

Dexlansoprazole is a Proton Pump Inhibitor. The mechanism of action of dexlansoprazole is as a Proton Pump Inhibitor.

DEXLANSOPRAZOLE

Various agents with different action mechanisms used to treat or ameliorate PEPTIC ULCER or irritation of the gastrointestinal tract. This has included ANTIBIOTICS to treat HELICOBACTER INFECTIONS; HISTAMINE H2 ANTAGONISTS to reduce GASTRIC ACID secretion; and ANTACIDS for symptomatic relief.

Compounds that inhibit H(+)-K(+)-EXCHANGING ATPASE. They are used as ANTI-ULCER AGENTS and sometimes in place of HISTAMINE H2 ANTAGONISTS for GASTROESOPHAGEAL REFLUX.

The dual delayed-release formulation of dexlansoprazole results in a plasma concentration-time profile with two distinct peaks; the first peak occurs one to two hours after administration, followed by a second peak within four to five hours. About 25% of the dose is released at the pH level of 5.5 in the proximal duodenum, while the other 75% is released in the distal small intestine at the pH level of 6.75. After oral administration of dexlansoprazole 30 or 60 mg to healthy subjects and symptomatic GERD patients, mean Cmax and AUC values of dexlansoprazole increased approximately dose-proportionally. Following administration of 30 mg in healthy adults, the mean (%CV) Cmax and AUC were 658 (40%) ng/mL and 3275 (47%) ng x h/mL, respectively. At a dose of 60 mg, the mean (%CV) Cmax and AUC were 1397 (51%) ng/mL and 6529 (60%) ng x h/mL, respectively. In healthy subjects, food increased Cmax by 12 to 55% and AUC by 9 to 37%. The effect of food on Tmax varied, as both an increase and a decrease was observed.

Dexlansoprazole does not appear to be eliminated unchanged in the urine. Following the administration of [14C] dexlansoprazole to six healthy male subjects, approximately 50.7% (standard deviation (SD): 9.0%) of the administered radioactivity was excreted in urine and 47.6% (SD: 7.3%) in the feces.

The apparent volume of distribution (Vz/F) after multiple doses in symptomatic GERD patients was 40 L.

Apparent clearance (CL/F) in healthy subjects was 11.4 to 11.6 L/hour, respectively, after five days of 30 or 60 mg once daily administration.