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-release formulation of dexlansoprazole results in two distinct peaks in its plasma concentration-time curve; the first peak occurs 1 to 2 hours after administration, and the second peak occurs 4 to 5 hours. Approximately 25% of the dose is released in the proximal duodenum at pH 5.5, and the remaining 75% is released in the distal small intestine at pH 6.75. Following oral administration of 30 or 60 mg dexlansoprazole in healthy subjects and patients with symptomatic gastroesophageal reflux disease (GERD), the mean Cmax and AUC of dexlansoprazole increased approximately dose-proportionally. In healthy adults, after administration of 30 mg, the mean (%CV) Cmax and AUC were 658 (40%) ng/mL and 3275 (47%) ng·h/mL, respectively. At the 60 mg dose, the mean (%CV) Cmax and AUC were 1397 (51%) ng/mL and 6529 (60%) ng·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 was mixed, with both increases and decreases observed. Dexlansoprazole does not appear to be excreted unchanged in the urine. In six healthy male subjects, approximately 50.7% (SD: 9.0%) of the radioactive material was excreted in the urine and 47.6% (SD: 7.3%) in the feces after administration of [14C]dexlansoprazole. The apparent volume of distribution (Vz/F) after multiple doses was 40 L in patients with symptomatic gastroesophageal reflux disease (GERD). The apparent clearance (CL/F) after five consecutive days of administration of 30 mg or 60 mg once daily in healthy subjects was 11.4 L/h and 11.6 L/h, respectively. Metabolism/Metabolites Dexlansoprazole is extensively metabolized in the liver. It undergoes oxidation and reduction reactions, followed by sulfation, glucuronidation, and glutathione conjugation to form inactive metabolites. Oxidative metabolites are formed by CYP2C19-mediated hydroxylation and CYP3A4-mediated sulfone oxidation. CYP2C19 is a polymorphic liver enzyme with three phenotypes for substrate metabolism: rapid metabolizer (1/1), intermediate metabolizer (1/mutant), and slow metabolizer (mutant/mutant). Regardless of the CYP2C19 metabolic state, dexlansoprazole is the major circulating component in plasma. In CYP2C19 intermediate and rapid metabolizers, the major plasma metabolite is 5-hydroxydxlansoprazole and its glucuronide conjugate; while in CYP2C19 slow metabolizers, the major plasma metabolite is dexlansoprazole sulfone. Known metabolites of lansoprazole include 5-hydroxylansoprazole and lansoprazole sulfone.

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Biological Half-Life>
The elimination half-life of dexlansoprazole is approximately 1 to 2 hours.

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In CYP2C19 rapid metabolizers (EM): The area under the plasma concentration-time curve (AUC) of dexlansoprazole (R-lansoprazole) is 1.8 ± 0.6 μg·h/mL, the maximum plasma concentration (Cmax) is 0.7 ± 0.2 μg/mL, and the terminal half-life (t1/2) is 1.5 ± 0.3 hours.
The AUC of its metabolite 5-hydroxylansoprazole was 3.2 ± 0.8 μg·h/mL [3]
- In the CYP2C19 intermediate metabolizer (IM): the AUC of dexlansoprazole (R-lansoprazole) was 3.5 ± 1.1 μg·h/mL, Cmax was 1.2 ± 0.4 μg/mL, and t1/2 was 2.3 ± 0.5 h. The AUC of 5-hydroxylansoprazole was 4.1 ± 1.0 μg·h/mL [3]
- In the CYP2C19 poor metabolizer (PM): the AUC of dexlansoprazole (R-lansoprazole) was 8.7 ± 2.4 μg·h/mL, Cmax was 2.5 ± 0.7 μg/mL, and t1/2 was 3.8 ± 0.9 h. The AUC of 5-hydroxylansoprazole is 2.8 ± 0.7 μg·h/mL[3]
- Metabolic pathway: R-lansoprazole is mainly metabolized by CYP2C19 to produce the active metabolite 5-hydroxylansoprazole; the metabolic rate varies significantly with CYP2C19 genotype (EM > IM > PM)[3]

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Dexlansoprazole is the R-enantiomer of the proton pump inhibitor lansoprazole. There is currently no information regarding the use of dexlansoprazole or lansoprazole during lactation. However, lansoprazole has been safely used in newborns, so the amount of dexlansoprazole in breast milk is unlikely to cause harm.
◉ Effects on Breastfed Infants
As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
A retrospective U.S. claims database study found an increased risk of gynecomastia in users of proton pump inhibitors.
A review article reported that a search of the European Medicines Agency database found one case of gynecomastia, no cases of galactorrhea, one case of breast pain, and one case of breast enlargement among cases associated with dexlansoprazole. A search of the WHO Global Pharmacovigilance Database revealed two cases of gynecomastia, no cases of galactorrhea, four cases of breast pain, and one case of breast enlargement associated with dexlansoprazole.
Protein Binding
In healthy subjects, the plasma protein binding rate of dexlansoprazole ranged from 96% to 99%, independent of concentration (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 compound belonging to the benzimidazole class. It is a new-generation proton pump inhibitor (PPI) used to treat symptoms associated with gastroesophageal reflux disease (GERD) and erosive esophagitis. Dexlansoprazole is the R-enantiomer of compound [DB00448], which consists of a racemic mixture of R- and S-enantiomers. Compared to older-generation PPIs (including [DB00213], [DB00338], and [DB00448]), dexlansoprazole possesses unique pharmacokinetic characteristics due to its sustained-release and dual-dose system: this is designed to address some limitations of older-generation PPIs, such as short plasma half-life and the need for mealtime administration. Dexlansoprazole inhibits the final step in gastric acid production by blocking (H+, K+)-ATPase enzymes. 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 is a substituted benzimidazole prodrug with selective and irreversible proton pump inhibitory activity. As a weak base, dexlansoprazole accumulates in the acidic environment of the secretory tubules of gastric parietal cells, where it is converted to its active sulfinamide form. This form binds to the cysteine sulfhydryl group on the luminal side of the proton pump H+/K+ ATPase, thereby inhibiting the activity of the pump and the secretion of H+ ions into the gastric lumen by parietal cells, the final step in gastric acid production. The R-isomer of lansoprazole is used to treat severe gastroesophageal reflux disease. See also: dexlansoprazole sesquihydrate (its active moiety). Lansoprazole (note moved to).

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Drug Indications
Dexlansoprazole is a proton pump inhibitor (PPI) indicated for: - Treatment of erosive esophagitis (EE) of all grades in patients aged 12 years and older, with a treatment duration of up to 8 weeks. - Maintenance of healed EE and relief of heartburn symptoms, with a treatment duration of up to 6 months in adults and up to 16 weeks in patients aged 12 to 17 years. - Treatment of heartburn symptoms in patients aged 12 years and older with symptomatic non-erosive gastroesophageal reflux disease (GERD), with a treatment duration of up to 4 weeks.

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Mechanism of Action
Dexlansoprazole inhibits gastric acid secretion by blocking the final step in gastric acid production. It inhibits H/K ATPase on the secretory surface of gastric parietal cells, an enzyme involved in hydrochloric acid secretion. H/K ATPase is a proton pump responsible for hydrolyzing ATP and exchanging H+ ions in the cytoplasm with K+ ions in the secretory tubules: this process leads to the secretion of hydrochloric acid into the gastric lumen.

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Pharmacodynamics
Dexlansoprazole is a proton pump inhibitor (PPI) that inhibits basal and stimulant gastric acid secretion. PPIs have a rebound effect and a risk of excessive gastric acid secretion in the short term; therefore, the use of dexlansoprazole cannot rule out this risk. Long-term use of PPIs is also associated with increased susceptibility to bacterial infections, vitamin B12 and iron deficiency, hypomagnesemia and hypocalcemia, all of which may lead to osteoporosis and fractures. Dexlansoprazole has been reported to interfere with secretin stimulation tests and cause false positive results in tetrahydrocannabinol urine screening tests. Dexlansoprazole can increase gastrin levels, thereby causing enterochromaffin cell proliferation and increasing serum CgA levels. Elevated CgA levels may lead to false positive results in neuroendocrine tumor diagnostic tests.

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Dexlansoprazole (R-lansoprazole) is the R-enantiomer of lansoprazole, which is a proton pump inhibitor[3].
- Its pharmacokinetic characteristics are significantly affected by CYP2C19 gene polymorphism: compared with fast metabolizers (homozygous wild-type CYP2C191 allele), slow metabolizers (homozygous CYP2C192 or 3 allele) exhibit significantly higher systemic exposures (AUC and Cmax) and longer half-lives[3].
- Due to reduced enzyme activity, the production of the major metabolite 5-hydroxylansoprazole is reduced in CYP2C19 slow metabolizers[3].

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.)