Sulfadiazine (SDZ)/trimethoprim (TMP; 30 mg of SDZ/TMP/kg of body weight) was given IV to the same 6 male calves at 1, 7, and 42 days of age and to 2 additional calves at 7 days of age. Serum concentrations of SDZ and TMP were best represented by a 2-compartment open model, but in 42-day-old calves, CSF concentrations of both drugs were best represented by a 1-compartment open model with first-order input. Between 1 and 42 days of age, the elimination half-life (t1/2(beta)) of SDZ decreased from 5.7 to 3.6 hours, and total body clearance (CLtot) increased from 1.43 to 1.88 ml/min/kg; the area under the curve (AUCo leads to x) decreased from 291.5 to 225.4 mg/L.h. The distribution coefficient (Vd(area)/kg of body weight) decreased with age, changing from 0.72 to 0.59 L/kg, between 1 and 42 days of age. Therapeutic concentrations of SDZ in serum (greater than 2 micrograms/ml) were maintained for 24 hours in 1-day-old calves and for about 15 hours in 7- and 42-day-old calves. The elimination rate of TMP increased about 9-fold; t1/2(beta) was 8.4, 2.1, and 0.9 hours, respectively, at 1, 7, and 42 days of age. Other values also reflected an increase in TMP elimination rate with age: CLtot increased from 2.8 to 12 to 28.9 ml/min/kg, k13 increased from 0.336 to 0.654 to 1.664/h and AUC(0 to infinity) decreased from 32.8 to 7.9 to 3.1 mg/L/h, respectively. Therapeutic concentrations (greater than 0.1 microgram/ml) were maintained for 15 hours, 8 hours, and about 6 hours in 1-, 7-, and 42-day-old calves, respectively. Penetration of SDZ and TMP into the CSF in 42-day-old calves was substantial; ratios of AUC(CSF)/AUCserum were 0.60 and 0.69, respectively. Therapeutic concentrations of drugs in CSF were maintained if serum concentrations were above therapeutic concentrations; elimination rates of both drugs from the CSF equaled those of serum. Sulfadiazine was excreted mainly unchanged; the percentage of dose excreted unchanged in 24 hours increased from 22.1 to 47.8 to 50.8% in 1-, 7-, and 42-day-old calves, respectively, paralleling the increase in CLtot. Trimethoprim was extensively biotransformed; the percentage of dose excreted unchanged in the urine in 24 hours decreased from 12.8 to 8.7 to 3.5%. Sulfadiazine and TMP were concentrated in the urine, and therapeutic concentrations of both drugs in urine were maintained for greater than 24 hours in calves of all ages.

Cephapirin (20 mg/kg of body weight, IV) was administered before and after 3 doses of probenecid (25, 50, or 75 mg/kg, intragastrically, at 12-hour intervals) to 2 mares. Clearance and apparent volume of distribution, based on area under the curve, were negatively correlated with probenecid dose. Clearance of cephapirin was decreased by approximately 50% by administration of 50 mg of probenecid/kg. Serum, synovial fluid, peritoneal fluid, CSF, urinary and endometrial concentrations of cephapirin were determined after 5 doses of cephapirin (20 mg/kg, IM, at 12-hour intervals) without and with concurrently administered probenecid (50 mg/kg, intragastrically) to 6 mares, including the 2 mares given cephapirin, IV. Highest mean serum cephapirin concentrations were 16.1 +/- 2.16 micrograms/ml at 0.5 hour after the 5th cephapirin dose [postinjection (initial) hour (PIH) 48.5] in mares not given probenecid and 23.7 +/- 1.30 micrograms/ml at 1.5 hours after the 5th cephapirin dose (PIH 49.5) in mares given probenecid. Mean peak peritoneal fluid and synovial fluid cephapirin concentrations were 6.2 +/- 0.57 micrograms/ml and 6.6 +/- 0.58 micrograms/ml, respectively, without probenecid administration and 12.3 +/- 0.46 micrograms/ml and 10 +/- 0.78 micrograms/ml, respectively, with concurrent probenecid administration. Mean trough cephapirin concentrations for peritoneal and synovial fluids in mares given probenecid were 2 to 3 times higher than trough concentrations in mares not given probenecid. Overall mean cephapirin concentrations were significantly higher for serum, peritoneal fluid, synovial fluid, and endometrium when probenecid was administered concurrently with cephapirin (P less than 0.01). Cephapirin was not detected in CSF samples. Overall mean urinary cephapirin concentrations (2.47 mg/ml without concurrent probenecid administration and 3.06 mg/ml with concurrent probenecid) were not significantly different (P greater than 0.05). Mean trough serum probenecid concentration was 61.2 +/- 5.28 micrograms/ml. Highest serum probenecid concentration was 148.8 +/- 5.97 micrograms/ml, 2 hours after the 5th cephapirin dose (PIH 50). Probenecid administration increased serum, synovial fluid, peritoneal fluid, and endometrial concentrations of cephapirin in mares.

Cerebrospinal fluid obtained from clinically normal free-ranging raccoons was analyzed and compared with CSF obtained from raccoons vaccinated orally with vaccinia-rabies glycoprotein (V-RG) recombinant virus vaccine and subsequently challenged peripherally with street rabies virus, and CSF from naive, rabies virus challenge-exposed control raccoons. Significant differences were not found in CSF of free-ranging or V-RG recombinant virus vaccine recipient raccoons, and there was no evidence of CNS invasion by V-RG virus. The CSF of naive, rabies challenge-exposed control raccoons contained high numbers of lymphocytes and monocytes, compatible with rabies virus encephalitis. Although V-RG orally vaccinated challenge-exposed raccoons were protected from lethal rabies virus infection, mild lymphocytic pleocytosis was evident at 90 days after challenge exposure.