Pharmacokinetics of sulfadiazine/trimethoprim in neonatal male calves: effect of age and penetration into cerebrospinal fluid.
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 (AUC0----infinity) 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 AUC0----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.(ABSTRACT TRUNCATED AT 250 WORDS)
Shoaf
S E
SE
Department of Pharmacology, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853-6401.
Schwark
W S
WS
Guard
C L
CL
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D000890:Anti-Infective Agents / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D002417:Cattle / Q000378:metabolism*; D004338:Drug Combinations / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D008297:Male; D013411:Sulfadiazine / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D014295:Trimethoprim / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D000096926:Benzenesulfonamides
D000890:Anti-Infective Agents; D004338:Drug Combinations; D013411:Sulfadiazine; D014295:Trimethoprim; C024873:sulfadiazine, trimethoprim drug combination; D000096926:Benzenesulfonamides