Ocular and serum disposition kinetics of cloxacillin after topical administration of benzathine cloxacillin and intravenous administration of sodium cloxacillin to calves

Disposition kinetics of cloxacillin were examined in calves after topical administration of benzathine cloxacillin and single IV administration of sodium cloxacillin, and the susceptibility of 17 field isolates of Moraxella bovis was measured. For the IV pharmacokinetic phase, sodium cloxacillin was administered at dosage of 10 mg/kg of body weight to male Holstein calves (n = 6, weighing 146 to 170 kg), and serum concentration of cloxacillin was measured thereafter for 10 hours. For the ocular pharmacokinetic phase, 6 calves were given either of 4 benzathine cloxacillin topical formulations consisting of 50-, 125-, 250-, or 375-mg doses. Treatment was repeated every 10 days until all 4 benzathine cloxacillin dosages were tested in the same 6 calves. Blood and tears were collected for 72 hours after each benzathine cloxacillin formulation was administered, and the concentration of cloxacillin in each specimen was measured, using a bioassay. The minimal inhibitory concentration of cloxacillin for 17 field isolates of M bovis was determined by use of an agar pour-plate dilution assay. After single IV administration of sodium cloxacillin, its half-life, body clearance, and volume of distribution were 19.5 +/- 12.8 minutes, 18.3 +/- 2.2 ml/min.kg, and 496 +/- 290 ml/kg, respectively. After topical administration of benzathine cloxacillin, cloxacillin concentration in lacrimal fluid peaked between 30 and 45 minutes and ranged between 963 microgram/ml and 3,256 microgram/ml for the 125- and 375- mg doses, respectively. There was no detectable cloxacillin activity in the lacrimal fluid of any calf by 36 hours after topical administration of benzathine cloxacillin, and cloxacillin was not detected in the serum at any time. The mean lacrimal fluid cloxacillin concentration for the 4 groups during the first 8 hours was not significantly different; however, by 12 hours, the cloxacillin concentration in tears from calves of the 250- and 375-mg groups was significantly (P < 0.05) greater than that in calves of the 50- and 125-mg groups. Cloxacillin concentration greater than or equal to 3.13 microgram/ml was maintained for a significantly (P < 0.05) longer time after treatment, using the 375-mg dose, compared with the 50-mg dose of benzathine cloxacillin. The minimal inhibitory concentration of cloxacillin for 1 isolate was 6.25 microgram/ml, but was less than or equal to 3.13 microgram/ml for 16 other M bovis isolates.