Validity of cycloheximide chylomicron flow blocking method for the evaluation of lymphatic transport of drugs
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F21%3A10429932" target="_blank" >RIV/00216208:11110/21:10429932 - isvavai.cz</a>
Alternative codes found
RIV/60461373:22340/21:43922890 RIV/00064203:_____/21:10429932 RIV/00064165:_____/21:10429932 RIV/00216208:11310/21:10429932
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=h_T4b4gfB1" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=h_T4b4gfB1</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/bph.15644" target="_blank" >10.1111/bph.15644</a>
Alternative languages
Result language
angličtina
Original language name
Validity of cycloheximide chylomicron flow blocking method for the evaluation of lymphatic transport of drugs
Original language description
BACKGROUND AND PURPOSE: Lymphatic transport of drugs after oral administration is an important mechanism for absorption of highly lipophilic compounds. Direct measurement in lymph duct cannulated animals is the gold standard method, but non-invasive cycloheximide chylomicron flow blocking method has gained popularity recently. However, concerns about its reliability have been raised. The aim of this work was to investigate the validity of cycloheximide chylomicron flow blocking method for the evaluation of lymphatic transport using model compounds with high to very high lipophilicity, i.e. abiraterone and cinacalcet. EXPERIMENTAL APPROACH: Series of pharmacokinetic studies were conducted with abiraterone acetate and cinacalcet hydrochloride after enteral/intravenous administration to intact, lymph duct cannulated, and/or cycloheximide pre-treated rats. KEY RESULTS: Mean total absolute oral bioavailability of abiraterone and cinacalcet was 7.0% and 28.7%, respectively. There was a large and significant overestimation of the lymphatic transport extent by the cycloheximide method. Mean relative lymphatic bioavailability of abiraterone and cinacalcet in cycloheximide method was 28-fold and 3-fold higher than in cannulation method, respectively. CONCLUSION AND IMPLICATIONS: Cycloheximide chylomicron flow blocking method did not provide reliable results on lymphatic absorption and substantially overestimated lymphatic transport for both molecules, i.e. abiraterone and cinacalcet. This non-invasive method should not be used for the assessment of lymphatic transport and previously obtained data should be critically revised.
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
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
British Journal of Pharmacology
ISSN
0007-1188
e-ISSN
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Volume of the periodical
178
Issue of the periodical within the volume
23
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
4663-4674
UT code for WoS article
000694932100001
EID of the result in the Scopus database
2-s2.0-85114638041