J 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

Odkazy

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

Štítky

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
Název: Preklinický a klinický výzkum studentů v oblasti farmakokinetiky, neuropsychofarmakologie a personalizované farmakoterapie v onkologii
Investor: Masarykova univerzita, Preklinický a klinický výzkum studentů v oblasti farmakokinetiky, neuropsychofarmakologie a personalizované farmakoterapie v onkologii, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty