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Quantitative analysis of the effect of probenecid on pharmacokinetics of 99mTc-mercaptoacetyltriglycine in dogs.
- Source :
-
Journal of veterinary pharmacology and therapeutics [J Vet Pharmacol Ther] 2005 Dec; Vol. 28 (6), pp. 559-64. - Publication Year :
- 2005
-
Abstract
- 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.
- Subjects :
- Animals
Area Under Curve
Female
Injections, Intravenous veterinary
Kidney Function Tests veterinary
Male
Probenecid administration & dosage
Radiopharmaceuticals blood
Technetium Tc 99m Mertiatide blood
Uricosuric Agents administration & dosage
Dogs metabolism
Probenecid pharmacology
Radiopharmaceuticals pharmacokinetics
Technetium Tc 99m Mertiatide pharmacokinetics
Uricosuric Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0140-7783
- Volume :
- 28
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of veterinary pharmacology and therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 16343289
- Full Text :
- https://doi.org/10.1111/j.1365-2885.2005.00699.x