BIOAVAILABILITY, DISPOSITION KINETICS AND DOSAGE OF SULFADIMETHOXINE IN DOGS

  • 1 January 1976
    • journal article
    • research article
    • Vol. 40  (3) , 310-317
Abstract
The disposition kinetics of sulfadimethoxine were studied in 6 normal beagle dogs after i.v. injection of a single dose (55 mg/kg). The median (range) distribution and elimination half times of the drug were 2.36 (2.06-3.35) h and 13.10 (9.71-16.50) h, respectively. Total body clearance of the drug had a median value of 21.7 ml/kg per h and a mean value of 21.4 ml/kg per h. While the overall tissue to plasma level ratio (k12/k21) of the drug was 0.55 after distribution equilibrium was attained, analogue computer simulated curves showed that at 24 h the fractions (percentage) of the dose in the central and tissue compartments were 12 and 11%, respectively. The drug was shown, by equilibrium dialysis, to be highly bound to plasma proteins (> 75%) within the usual therapeutic range (50-150 .mu.g/ml) of plasma levels. The systemic availability of sulfadimethoxine from the oral suspension was 32.8% (22.5-80.0). Since the absorption half time, 1.87 (0.86-3.22) h, was considerably shorter than the half-life, 13.10 (9.71-16.50) h, of the drug, the rate of absorption would have little influence on the dosage regimen. Based on the experimental data obtained, a satisfactory dosage regimen might consist of a priming dose of 55 mg/kg by the i.v. route and maintenance doses of either 27.5 mg/kg of sulfadimethoxin injection given i.v. or 55 mg/kg of the oral suspension administered at 24 h intervals. The adequacy and duration of therapy will depend upon the clinical response obtained.