Quantitative analysis of the effect of probenecid on pharmacokinetics of 99m Tc‐mercaptoacetyltriglycine in dogs

Effect of probenecid on pharmacokinetics of 99m Tc‐mercaptoacetylytriglycine ( 99m 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 99m Tc‐MAG 3 were described with a two‐compartment open model. Plasma 99m 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 dss , 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 dss decreased Cl p significantly. Cl p was a function of plasma probenecid concentration based on Michaelis–Menten kinetics. The maximum Cl p inhibition ( I max ) by probenecid and the plasma probenecid concentration that induced 50% of I max ( I 50 ) were estimated to be 72 ± 12% and 13 ± 8  μ g/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 99m Tc‐MAG 3 and body weight are discussed.