Comparison of screening methods for determination of N4-acetyltransferase capacity (acetylator phenotype) in outbred rabbit strains
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Abstract:
The low incidence (10% to 35%) of slow acetylator phenotype requires development of efficient screening techniques for phenotyping rabbits. We report here the phenotyping of 166 rabbits by means of an IA calculated from the plasma determination of SDZ and NSDZ at 60 min after a dose of 20 mg/kg SDZ intravenously. The IA is compared to the elimination t 1/2 beta of SDZ as well as with other parameters. CITB and present of dose recovered in urine as NSDZ. The use of IA to screen for slow or fast acetylators when compared to t1/2 beta resulted in six rabbits being misclassified (13.3%); the use of CITB values from the same animals resulted in two misclassifications (4.4%); the use of percent of dose recovered in urine as NSDZ resulted in only one rabbit being misclassified (3.8%). We conclude that the IA provides an efficient screening procedure for acetylation phenotype in the rabbit with the further advantage that it can be performed as part of the definitive t1/2 beta determination, avoiding double handling of rabbits.