Quantitative analysis of the effect of probenecid on pharmacokinetics of 99mTc-mercaptoacetyltriglycine in dogs

Autor: Naoaki Yamada, G. B. Daniel, M. Hashimoto, Y. Yokoyama, Takehiko Kakizaki, Nobuhiko Ito, K. Sato, Masahiro Natsuhori
Rok vydání: 2005
Předmět:
Zdroj: Journal of veterinary pharmacology and therapeutics. 28(6)
ISSN: 0140-7783
Popis: Effect of probenecid on pharmacokinetics of 9 9 m Tc-mercaptoacetylytriglycine ( 9 9 m Tc-MAG 3 ) in dogs was investigated before (control), and after 15 min and 24 h of i.v. injection of probenecid (20 mg/kg). Plasma concentration-time profiles of 9 9 m Tc-MAG 3 were described with a two-compartment open model. Plasma 9 9 m Tc-MAG 3 clearances (Cl p , ml/min/kg) were 7.9 ′ 0.5, 3.3 ′ 0.5 and 4.8 ′ 1.3 in control, 15 min and 24 h after probenecid administration respectively. Similarly, the biological half-lives at elimination phase (t 1 / 2 , h) were 0.61 ′ 0.09, 0.79 ′ 0.11 and 0.74 ′ 0.12, and volumes of distribution at steady state (V d s s , L/kg) were 0.29 ′ 0.04, 0.20 ′ 0.05 and 0.25 ′ 0.06 respectively. The prolonged biological half-life and decreased V d s s decreased Cl p significantly. Cl p was a function of plasma probenecid concentration based on Michaelis-Menten kinetics. The maximum Cl p inhibition (I m a x ) by probenecid and the plasma probenecid concentration that induced 50% of I m a x (I 5 0 ) were estimated to be 72 ′ 12% and 13 ′ 8 μg/ml respectively. This means that the rest (about 28%) of the Cl p is not blocked by probenecid alone, suggesting the possibility of another route(s) of elimination or renal transporters which are independent from probenecid. Moreover, inter-species correlation between Cl p of 9 9 m Tc-MAG 3 and body weight are discussed.
Databáze: OpenAIRE
Externí odkaz: