2020
Improved Pharmacokinetics and Tissue Uptake of Complexed Daidzein in Rats
KWIECIEN, Anna, Jana RUDÁ, Kamil KAMINSKI, Zuzana BABINSKÁ, Iwona POPIOLEK et. al.Základní údaje
Originální název
Improved Pharmacokinetics and Tissue Uptake of Complexed Daidzein in Rats
Název česky
Výhodná farmakokinetika a vstup do tkání u daidzeinu ve formě komplexu u potkana
Autoři
KWIECIEN, Anna (616 Polsko), Jana RUDÁ (203 Česká republika, garant, domácí), Kamil KAMINSKI (616 Polsko), Zuzana BABINSKÁ (703 Slovensko, domácí), Iwona POPIOLEK (616 Polsko), Krzysztof SZCZUBIALKA (616 Polsko), Maria NOWAKOWSKA (616 Polsko) a Maria WALCZAK (616 Polsko)
Vydání
Pharmaceutics, ST ALBAN-ANLAGE, MDPI, 2020, 1999-4923
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30104 Pharmacology and pharmacy
Stát vydavatele
Švýcarsko
Utajení
není předmětem státního či obchodního tajemství
Impakt faktor
Impact factor: 6.321
Kód RIV
RIV/00216224:14110/20:00115616
Organizační jednotka
Lékařská fakulta
UT WoS
000519268500097
Klíčová slova anglicky
daidzein; gamma-cyclodextrin; bioavailability; nonlinear pharmacokinetics; tissue uptake
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 14. 7. 2020 14:58, Mgr. Tereza Miškechová
Anotace
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.
Návaznosti
MUNI/A/1292/2019, interní kód MU |
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