Development of a physiologic-based pharmacokinetic model for estimating sulfamethazine concentrations in swine and application to prediction of violative residues in edible tissues

被引:36
作者
Buur, JL [1 ]
Baynes, RE
Craigmill, AL
Riviere, JE
机构
[1] N Carolina State Univ, Coll Vet Med, Ctr Chem Toxicol Res & Pharmacokinet, Food Anim Residue Avoidance Bank,Dept Populat Hlt, Raleigh, NC 27605 USA
[2] Univ Calif Davis, Coll Agr & Environm Sci, Dept Environm Toxicol, Food Anim Residue Avoidance Databank, Davis, CA 95616 USA
关键词
D O I
10.2460/ajvr.2005.66.1686
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
Objective-To develop a flow-limited, physiologic-based pharmacokinetic model for use in estimating concentrations of sulfamethazine after IV administration to swine. 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 (FARAD). 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.
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页码:1686 / 1693
页数:8
相关论文
共 27 条
[1]  
[Anonymous], 2001, Biology of the Domestic Pig
[2]  
Brocklebank JR, 1997, CAN VET J, V38, P645
[3]   Physiologically based pharmacokinetic modeling as a tool for drug development [J].
Charnick, SB ;
Kawai, R ;
Nedelman, JR ;
Lemaire, M ;
Niederberger, W ;
Sato, H .
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS, 1995, 23 (02) :217-229
[4]  
Clewell HJ, 1997, J TOXICOL ENV HEALTH, V52, P475
[5]   A physiologically based pharmacokinetic model for oxytetracycline residues in sheep [J].
Craigmill, AL .
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS, 2003, 26 (01) :55-63
[6]  
Damian P, 1997, J AM VET MED ASSOC, V210, P633
[7]   PHYSIOLOGICAL MODEL FOR DISTRIBUTION OF SULFATHIAZOLE IN SWINE [J].
DUDDY, J ;
HAYDEN, TL ;
BOURNE, DWA ;
FISKE, WD ;
BENEDEK, IH ;
STANLEY, D ;
GONZALEZ, A ;
HEIERMAN, W .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1984, 73 (11) :1525-1528
[8]  
ENTRIKEN TL, 2001, VET PHARM BIOL, P2114
[9]   Feasibility of using half-life multipliers to estimate extended withdrawal intervals following the extralabel use of drugs in food-producing animals [J].
Gehring, R ;
Baynes, RE ;
Craigmill, AL ;
Riviere, JE .
JOURNAL OF FOOD PROTECTION, 2004, 67 (03) :555-560
[10]   Application of a physiologically based pharmacokinetic model for reference dose and reference concentration estimation for acetone [J].
Gentry, PR ;
Covington, TR ;
Clewell, H ;
Anderson, ME .
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, 2003, 66 (23) :2209-2225