Quantitative analysis of the effect of probenecid on pharmacokinetics of 99mTc-mercaptoacetyltriglycine in dogs.
Effect of probenecid on pharmacokinetics of 99mTc-mercaptoacetylytriglycine (99mTc-MAG3) 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 99mTc-MAG3 were described with a two-compartment open model. Plasma 99mTc-MAG3 clearances (Clp, 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 (Vdss, L/kg) were 0.29 +/- 0.04, 0.20 +/- 0.05 and 0.25 +/- 0.06 respectively. The prolonged biological half-life and decreased Vdss decreased Clp significantly. Clp was a function of plasma probenecid concentration based on Michaelis-Menten kinetics. The maximum Clp inhibition (Imax) by probenecid and the plasma probenecid concentration that induced 50% of Imax (I50) were estimated to be 72 +/- 12% and 13 +/- 8 microg/ml respectively. This means that the rest (about 28%) of the Clp 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 Clp of 99mTc-MAG3 and body weight are discussed.
Kakizaki
T
T
Laboratory of Veterinary Radiology and Radiation Biology, School of Veterinary Medicine and Animal Sciences, Kitasato University, Towada, Aomori, Japan.
Yokoyama
Y
Y
Natsuhori
M
M
Yamada
N
N
Hashimoto
M
M
Sato
K
K
Ito
N
N
Daniel
G B
GB
D000818:Animals; D019540:Area Under Curve; D004285:Dogs / Q000378:metabolism*; D005260:Female; D007275:Injections, Intravenous / Q000662:veterinary; D007677:Kidney Function Tests / Q000662:veterinary; D008297:Male; D011339:Probenecid / Q000008:administration & dosage / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics*; D017263:Technetium Tc 99m Mertiatide / Q000097:blood / Q000493:pharmacokinetics*; D014528:Uricosuric Agents / Q000008:administration & dosage / Q000494:pharmacology*
D019275:Radiopharmaceuticals; D014528:Uricosuric Agents; D017263:Technetium Tc 99m Mertiatide; D011339:Probenecid