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Pharmacokinetics of cefotaxime and probenecid in sheep with normal and reduced renal function
Author(s) -
GUERRINI V. H.,
FILIPPICH L.J.,
ENGLISH P. B.,
CAO G. R.,
BOURNE D. W. A.
Publication year - 1984
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.1984.tb00913.x
Subject(s) - probenecid , volume of distribution , chemistry , pharmacokinetics , elimination rate constant , renal function , cefotaxime , endocrinology , medicine , excretion , distribution (mathematics) , distribution volume , renal physiology , pharmacology , antibiotics , biochemistry , mathematical analysis , mathematics
The pharmacokinetics of cefotaxime and probenecid, given by intravenous injection, were determined in six Merino ewes which had been subjected to a 75% reduction in renal mass. These results were compared with results previously determined in sheep with normal renal function. In the sheep with reduced renal mass, the following significant changes in parameter values for cefotaxime were observed. The elimination rate constant (k el ) decreased by 47%, the apparent volume of the central compartment (V c ) decreased by 59%, the steady state volume (V ss ) decreased by 50%, and the total body clearance (Cl B ) decreased by 78%. The rate constant for distribution of drug into tissues (k 12 ) increased 6.9 times, the rate constant for distribution out of tissues (k 21 ) increased 3.7 times, and the area under the plasma concentration‐time curve ( AUC) increased by a factor of 4.9. The parameter values, determined in sheep with reduced renal mass, for probenecid plasma half‐life, V ss and the rate constants k 12 , k 21 and k el were not significantly different from the values obtained previously in sheep with normal renal mass. However, the rate constant for renal excretion of probenecid (k c) , renal clearance (Cl R ), Cl B and V c decreased by 79, 90, 54 and 36%, respectively. The results indicate that reduced renal mass increased the plasma half‐life for cefotaxime as well as increasing its diffusion into tissue. In the case of probenecid the overall distribution and elimination kinetics were not altered by reduced renal mass; however, the rate of urinary excretion of the drug was reduced.