Pharmacokinetics of sulfadiazine/trimethoprim in neonatal male calves: effect of age and penetration into cerebrospinal fluid

• Published in: American journal of veterinary research Vol. 50; no. 3; p. 396
• Main Authors: Shoaf, S.E, Schwark, W.S, Guard, C.L
• Format: Journal Article
• Language: English
• Published: United States 01.03.1989
• Subjects: AGE; Age Factors; Animals; Animals, Newborn - metabolism; Anti-Infective Agents - cerebrospinal fluid; Anti-Infective Agents - pharmacokinetics; Cattle - metabolism; Drug Combinations - cerebrospinal fluid; Drug Combinations - pharmacokinetics; EDAD; FARMACOLOGIA; FLUIDO CEREBROESPINAL; INFANTES; LIQUIDE CEPHALORACHIDIEN; Male; NOUVEAU-NE; PHARMACOLOGIE; Sulfadiazine - cerebrospinal fluid; Sulfadiazine - pharmacokinetics; SULFAMIDE; SULFONAMIDAS; TERAPEUTICA MEDICAMENTOSA; TERNERO; THERAPEUTIQUE MEDICAMENTEUSE; Trimethoprim - cerebrospinal fluid; Trimethoprim - pharmacokinetics; TRIMETHOPRIME; TRIMETROPINA; VEAU
• ISSN: 0002-9645; 1943-5681

Sulfadiazine (SDZ)/trimethoprim (TMP; 30 mg of SDZ/TMP/kg of body weight) was given to the same 6 male calves at 1, 7, and 42 ds of age and to 2 additional calves at 7 ds 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 hs, 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 ( 2 micrograms/ml) were maintained for 24 hs in 1-day-old calves and for about 15 hs 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 hs, resp. at 1, 7, and 42 ds 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, resp. Therapeutic concentrations ( 0.1 microgram/ml) were maintained for 15 hs, 8 hs, and about 6 hs in 1-, 7-, and 42-day-old calves, resp. 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, resp. 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 hs increased from 22.1 to 47.8 to 5 0.8% in 1-, 7-, and 42-day-old calves, resp. paralleling the increase in CLtot