July 1991
Volume 32, Issue 8
Articles  |   July 1991
Characterization of arylamine acetyltransferase in the rabbit eye.
Author Affiliations
  • D A Campbell
    College of Pharmacy, University of Iowa, Iowa City 52242.
  • R D Schoenwald
    College of Pharmacy, University of Iowa, Iowa City 52242.
  • M W Duffel
    College of Pharmacy, University of Iowa, Iowa City 52242.
  • C F Barfknecht
    College of Pharmacy, University of Iowa, Iowa City 52242.
Investigative Ophthalmology & Visual Science July 1991, Vol.32, 2190-2200. doi:
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      D A Campbell, R D Schoenwald, M W Duffel, C F Barfknecht; Characterization of arylamine acetyltransferase in the rabbit eye.. Invest. Ophthalmol. Vis. Sci. 1991;32(8):2190-2200.

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      © ARVO (1962-2015); The Authors (2016-present)

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The activity of arylamine acetyltransferase with p-aminobenzoic acid (PABA), sulfamethazine (SMZ), and aminozolamide as substrates was studied in rabbit tissue homogenates of the corneal epithelium, stroma-endothelium, iris-ciliary process, and liver. Rabbits were classified as rapid or slow acetylators with respect to their rate of hepatic acetylation of SMZ. The ocular disposition of aminozolamide in the two phenotypes was compared using a topical ocular infusion method that permitted a constant concentration to remain in contact with the intact cornea. The effect of hepatic-acetylator phenotype on the intraocular pressure (IOP) recovery rate and drug concentrations in tissues after single-dose administration of aminozolamide also was studied. In general, the rank order of arylamine acetyltransferase activity regardless of substrate was liver greater than iris-ciliary process greater than corneal epithelium greater than stroma-endothelium. The specific activity with aminozolamide as substrate was greater than that with SMZ in each tissue homogenate and greater than with PABA as substrate in all tissues except the stroma-endothelium of slow hepatic-acetylator rabbits. Very low enzyme activity ratios for ocular acetylation between rapid and slow hepatic-acetylating rabbits indicated that acetylation in the ocular tissues did not correspond with the acetylation phenotype. At various times during and after topical infusion to the anesthetized rabbit, assay determinations of drug and metabolite in ocular tissues indicated that there were no significant differences between phenotypes in the disposition of either drug or metabolite. These results correlate with the IOP measurements after topical infusion; they also showed no difference in the effect of aminozolamide between hepatic-acetylator phenotypes. These results indicate that the ocular disposition and the decrease in IOP from topical application of aminozolamide is independent of the hepatic-acetylation phenotype in the rabbit. There are significant amounts of acetyltransferase activity in the ocular tissues of the rabbit with these three substrates, indicating that acetylation may be occurring for other arylamine drugs used in the eye.


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