In all three CYP2C19 genotype groups, the plasma concentrations of (R)-lansoprazole are significantly higher than those of the corresponding (S)-enantiomer. For all three genotype groups, the (R)-lansoprazole's AUC0-∞ Cmax and elimination half-life are considerably longer and higher, respectively, than those of the (S)-enantiomer[3].

Absorption, Distribution and Excretion
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.

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Metabolism / Metabolites
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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Biological Half-Life
Dexlansoprazole is eliminated with a half-life of approximately one to two hours.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Dexlansoprazole is the R-enantiomer of the proton-pump inhibitor, lansoprazole. No information is available on the use of dexlansoprazole or lansoprazole during breastfeeding. However, lansoprazole has been used safely in newborn infants, so it is unlikely that the amount of dexlansoprazole in breastmilk would be harmful.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
A retrospective claims database study in the United States found that users of proton pump inhibitors had an increased risk of gynecomastia.
A review article reported that a search of database from the European Pharmacovigilance Centre found 1 case of gynecomastia, no cases of galactorrhea, 1 cases of breast pain and 1 case of breast enlargement associated with dexlansoprazole. A search of the WHO global pharmacovigilance database found 2 cases of gynecomastia, no cases of galactorrhea, 4 cases of breast pain and 1 case of breast enlargement associated with dexlansoprazole.

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Protein Binding
Plasma protein binding of dexlansoprazole ranged from 96 to 99% in healthy subjects and was independent of concentration from 0.01 to 20 mcg/mL.

[1]. Effects of lansoprazole on pharmacokinetics and metabolism of theophylline. Eur J Clin Pharmacol, 1995. 48(5): p. 391-5.

[2]. Advances in the discovery of exosome inhibitors in cancer. J Enzyme Inhib Med Chem. 2020 Dec;35(1):1322-1330.

[3]. Pharmacokinetic differences between the enantiomers of lansoprazole and its metabolite, 5-hydroxylansoprazole, in relation to CYP2C19 genotypes. Eur J Clin Pharmacol. 2004 Nov;60(9):623-8.

Dexlansoprazole is a sulfoxide and a member of benzimidazoles.
Dexlansoprazole is a new-generation proton pump inhibitor (PPI) used for the management of symptoms associated with gastroesophageal reflux disease (GERD) and erosive esophagitis. Dexlansoprazole is the R-enantiomer of [DB00448], which is composed of a racemic mixture of the R- and S-enantiomers. Compared to the older generation of PPIs (which includes [DB00213], [DB00338], and [DB00448]), dexlansoprazole has a unique pharmacokinetic profile due to its delayed-release and dual-delivery release system: This aims to address some limitations of the older-generation PPIs, such as short plasma half-life and the need for meal-associated dosing. Dexlansoprazole inhibits the final step in gastric acid production by blocking the (H+, K+)-ATPase enzyme.
Dexlansoprazole is a Proton Pump Inhibitor. The mechanism of action of dexlansoprazole is as a Proton Pump Inhibitor.
Dexlansoprazole is the R-isomer of lansoprazole and a substituted benzimidazole prodrug with selective and irreversible proton pump inhibitor activity. As a weak base, dexlansoprazole accumulates in the acidic environment of the secretory canaliculus of the gastric parietal cell where it is converted to an active sulfenamide form that binds to cysteine sulfhydryl groups on the luminal aspect of the proton pump hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase), thereby inhibiting the pump's activity and the parietal cell secretion of H+ ions into the gastric lumen, the final step in gastric acid production.
The R-isomer of lansoprazole that is used to treat severe GASTROESOPHAGEAL REFLUX DISEASE.
See also: Dexlansoprazole Sesquihydrate (is active moiety of); Lansoprazole (annotation moved to).

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Drug Indication
Dexlansoprazole is a proton pump inhibitor (PPI) indicated for the: - Healing of all grades of erosive esophagitis (EE) for up to eight weeks in patients 12 years of age and older. - Maintenance of healed EE and relief of heartburn for up to six months in adults and 16 weeks in patients 12 to 17 years of age. - Treatment of heartburn associated with symptomatic non-erosive gastroesophageal reflux disease (GERD) for four weeks in patients 12 years of age and older.

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Mechanism of Action
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.

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Pharmacodynamics
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.

C16H14F3N3O2S

369.36

369.075

138530-94-6

Lansoprazole;103577-45-3;(R)-Lansoprazole-d4;(S)-Lansoprazole;138530-95-7

9578005

White to off-white solid powder

1.5±0.1 g/cm3

555.8±60.0 °C at 760 mmHg

66-68?C

289.9±32.9 °C

0.0±1.5 mmHg at 25°C

1.635

2.76

1

8

5

25

480

1

CC1=C(C=CN=C1C[S@@](=O)C2=NC3=CC=CC=C3N2)OCC(F)(F)F

MJIHNNLFOKEZEW-RUZDIDTESA-N

InChI=1S/C16H14F3N3O2S/c1-10-13(20-7-6-14(10)24-9-16(17,18)19)8-25(23)15-21-11-4-2-3-5-12(11)22-15/h2-7H,8-9H2,1H3,(H,21,22)/t25-/m1/s1

(R)-2-(((3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazole

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.77 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)