Dasatinib anhydrate containing oral formulation improves variability and bioavailability in humans
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F23%3A10469689" target="_blank" >RIV/00064165:_____/23:10469689 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/23:10469689
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=QioRebxM-x" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=QioRebxM-x</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41375-023-02045-1" target="_blank" >10.1038/s41375-023-02045-1</a>
Alternative languages
Result language
angličtina
Original language name
Dasatinib anhydrate containing oral formulation improves variability and bioavailability in humans
Original language description
Dasatinib monohydrate indicated for the treatment of chronic myeloid leukemia displays pH-dependent solubility. The aim of reported development program of novel dasatinib anhydrate containing formulation was to demonstrate improved absorption and lower pharmacokinetic variability compared to dasatinib monohydrate. In a bioavailability study comparing formulations containing 110.6 mg and 140 mg of dasatinib as anhydrate and monohydrate, respectively, both C-max and AUC of dasatinib were within standard 80.00-125.00% range, while the intra- and inter-subject variability for AUC(0-inf )after the test product was approximately 3-fold and 1.5-fold less than after the reference, respectively.In a drug-drug interaction study, omeprazole 40 mg reduced the mean AUC(0-inf) of dasatinib by 19%, when the test was ingested 2 h before the 5th omeprazole dose. This decrease of exposure is clinically irrelevant and substantially less than after the reference. Co-prescription analysis supports the importance of pH-dependent solubility of dasatinib, as >21% of patients were treated concomitantly with a PPI and dasatinib despite warnings against this co-medication in the SmPC.The novel dasatinib anhydrate containing formulation demonstrated improved absorption and less pharmacokinetic variability compared to dasatinib monohydrate product, which may translate into improved clinical outcomes, although this needs to be proven by an appropriate trial.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Leukemia
ISSN
0887-6924
e-ISSN
1476-5551
Volume of the periodical
37
Issue of the periodical within the volume
12
Country of publishing house
GB - UNITED KINGDOM
Number of pages
7
Pages from-to
2486-2492
UT code for WoS article
001076936500001
EID of the result in the Scopus database
2-s2.0-85173069639