Detailed Information on Publication Record
2020
Improved Pharmacokinetics and Tissue Uptake of Complexed Daidzein in Rats
KWIECIEN, Anna, Jana RUDÁ, Kamil KAMINSKI, Zuzana BABINSKÁ, Iwona POPIOLEK et. al.Basic information
Original name
Improved Pharmacokinetics and Tissue Uptake of Complexed Daidzein in Rats
Name in Czech
Výhodná farmakokinetika a vstup do tkání u daidzeinu ve formě komplexu u potkana
Authors
KWIECIEN, Anna (616 Poland), Jana RUDÁ (203 Czech Republic, guarantor, belonging to the institution), Kamil KAMINSKI (616 Poland), Zuzana BABINSKÁ (703 Slovakia, belonging to the institution), Iwona POPIOLEK (616 Poland), Krzysztof SZCZUBIALKA (616 Poland), Maria NOWAKOWSKA (616 Poland) and Maria WALCZAK (616 Poland)
Edition
Pharmaceutics, ST ALBAN-ANLAGE, MDPI, 2020, 1999-4923
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
30104 Pharmacology and pharmacy
Country of publisher
Switzerland
Confidentiality degree
není předmětem státního či obchodního tajemství
Impact factor
Impact factor: 6.321
RIV identification code
RIV/00216224:14110/20:00115616
Organization unit
Faculty of Medicine
UT WoS
000519268500097
Keywords in English
daidzein; gamma-cyclodextrin; bioavailability; nonlinear pharmacokinetics; tissue uptake
Tags
International impact, Reviewed
Změněno: 14/7/2020 14:58, Mgr. Tereza Miškechová
Abstract
V originále
The pharmacokinetic profile and tissue uptake of daidzein (DAI) was determined in rat serum and tissues (lungs, eyes, brain, heart, spleen, fat, liver, kidney, and testes) after intravenous and intraperitoneal administration of DAI in suspension or complexed with ethylenediamine-modified gamma-cyclodextrin (GCD-EDA/DAI). The absolute and relative bioavailability of DAI suspended (20 mg/kg i.v. vs. 50 mg/kg i.p.) and complexed (0.54 mg/kg i.v. vs. 1.35 mg/kg i.p.) was determined. After i.p. administration, absorption of DAI complexed with GCD-EDA was more rapid (t(max) = 15 min) than that of DAI in suspension (t(max) = 45 min) with a ca. 3.6 times higher maximum concentration (C-max = 615 vs. 173 ng/mL). The i.v. half-life of DAI was longer in GCD-EDA/DAI complex compared with DAI in suspension (t(0.5) = 380 min vs. 230 min). The volume of distribution of DAI given i.v. in GCD-EDA/DAI complex was ca. 6 times larger than DAI in suspension (38.6 L/kg vs. 6.2 L/kg). Our data support the concept that the pharmacokinetics of DAI suspended in high doses are nonlinear. Increasing the intravenous dose 34 times resulted in a 5-fold increase in AUC. In turn, increasing the intraperitoneal dose 37 times resulted in a ca. 2-fold increase in AUC. The results of this study suggested that GCD-EDA complex may improve DAI bioavailability after i.p. administration. The absolute bioavailability of DAI in GCD-EDA inclusion complex was ca. 3 times greater (F = 82.4% vs. 28.2%), and the relative bioavailability was ca. 21 times higher than that of DAI in suspension, indicating the need to study DAI bioavailability after administration by routes other than intraperitoneal, e.g., orally, subcutaneously, or intramuscularly. The concentration of DAI released from GCD-EDA/DAI inclusion complex to all the rat tissues studied was higher than after administration of DAI in suspension. The concentration of DAI in brain and lungs was found to be almost 90 and 45 times higher, respectively, when administered in complex compared to the suspended DAI. Given the nonlinear relationship between DAI bioavailability and the dose released from the GCD-EDA complex, complexation of DAI may thus offer an effective approach to improve DAI delivery for treatment purposes, for example in mucopolysaccharidosis (MPS), allowing the reduction of ingested DAI doses.
Links
| MUNI/A/1292/2019, interní kód MU |
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