Effect of probenecid on the pharmacokinetics of cefotaxime in sheep

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Abstract
The effect of probenecid given i.v. i.m. and s.c. injection on the pharmacokinetics of cefotaxime was studied in 6 Merino ewes. When given i.v. probenecid increased significantly (P < 0.05) the plasma half-life of cefotaxime 3-fold (to 0.94 .+-. 0.32 h) and the area under the curve (AUC) approximately 2-fold (to 41.1 .+-. 16.8 .mu.g.h/ml), and decreased plasma cefotaxime clearance (ClB) 45% (to 0.648 .+-. 0.191 I/h/kg). When given with probenecid i.v., renal clearance (CLR), volume of the central compartment (VC), volume of distribution steady state (Vd(ss)), and the amount excreted in urine unchanged did not alter significantly. When given by i.m. [intramuscular] injection, probenecid and cefotaxime were well tolerated and cefotaxime was well absorbed (101 .+-. 45%). When given by s.c. injection, only 40 .+-. 25% cefotaxime was absorbed. When given i.m. or s.c. probenecid appeared to reduce the ClB and ClR of cefotaxime, probably because plasma probenecid concentrations are prolonged. Probenecid did not appear to affect the distribution of cefotaxime.