Objective—To develop a flow-limited, physiologicbased
pharmacokinetic model for use in estimating
concentrations of sulfamethazine after IV administration
Sample Population—4 published studies provided
physiologic values for organ weights, blood flows,
clearance, and tissue-to-blood partition coefficients,
and 3 published studies provided data on plasma and
other tissue compartments for model validation.
Procedure—For the parent compound, the model
included compartments for blood, adipose, muscle,
liver, and kidney tissue with an extra compartment
representing the remaining carcass. Compartments
for the N-acetyl metabolite included the liver and the
remaining body. The model was created and optimized
by use of computer software. Sensitivity
analysis was completed to evaluate the importance
of each constant on the whole model. The model was
validated and used to estimate a withhold interval
after an IV injection at a dose of 50 mg/kg. The withhold
interval was compared to the interval estimated
by the Food Animal Residue Avoidance Databank
Results—Specific tissue correlations for plasma, adipose,
muscle, kidney, and liver tissue compartments
were 0.93, 0.86, 0.99, 0.94, and 0.98, respectively.
The model typically overpredicted concentrations at
early time points but had excellent accuracy at later
time points. The withhold interval estimated by use of
the model was 120 hours, compared with 100 hours
estimated by FARAD.
Conclusions and Clinical Relevance—Use of this
model enabled accurate prediction of sulfamethazine
pharmacokinetics in swine and has applications for
food safety and prediction of drug residues in edible
tissues. (Am J Vet Res 2005;66:1686–1693)
Objective—To describe the pharmacokinetics of N-acetylcysteine (NAC) in healthy cats after oral and IV administration.
Animals—6 healthy cats.
Procedures—In a crossover study, cats received NAC (100 mg/kg) via IV and oral routes of administration; there was a 4-week washout period between treatments. Plasma samples were obtained at 0, 5, 15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 36, and 48 hours after administration, and NAC concentrations were quantified by use of a validated high-performance liquid chromatography–mass spectrometry protocol. Data were analyzed via compartmental and noncompartmental pharmacokinetic analysis.
Results—Pharmacokinetics for both routes of administration were best described by a 2-compartment model. Mean ± SD elimination half-life was 0.78 ± 0.16 hours and 1.34 ± 0.24 hours for the IV and oral routes of administration, respectively. Mean bioavailability of NAC after oral administration was 19.3 ± 4.4%.
Conclusions and Clinical Relevance—The pharmacokinetics of NAC for this small population of healthy cats differed from values reported for humans. Assuming there would be similar pharmacokinetics in diseased cats, dose extrapolations from human medicine may result in underdosing of NAC in cats with acute disease. Despite the low bioavailability, plasma concentrations of NAC after oral administration at 100 mg/kg may be effective in the treatment of chronic diseases.