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Disposition of drugs in cystic fibrosis. VII. Acetylation of sulfamethoxazole in blood cells: In vitro‐in vivo correlation and characterization of its kinetics of acetylation in lymphocytes
Author(s) -
Hutabarat Renta M,
Smith Arnold L,
Unadkat Jashvant D
Publication year - 1994
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1994.52
Subject(s) - acetylation , cystic fibrosis , in vivo , chemistry , medicine , immunology , biochemistry , biology , microbiology and biotechnology , gene
Objective To determine if acetylation of sulfamethoxazole in blood cells is a surrogate measure of its acetylation in vivo. If it is, to use these cells to determine the mechanism(s) by which acetylation of sulfamethoxazole is enhanced in cystic fibrosis. Methods Single‐point sulfamethoxazole acetylation activity in blood cells obtained from patients with cystic fibrosis ( n = 6) and control subjects ( n = 7) who had previously participated in our in vivo study was determined. The parameters, V max and K m , for acetylation of sulfamethoxazole in lysed lymphocytes obtained from patients with cystic fibrosis ( n = 6) and control subjects ( n = 5) were also determined. Results The acetylation activity in cystic fibrosis whole blood, lysed erythrocytes, and lysed peripheral blood mononudear cells was significantly ( p < 0.05) greater than that in cells obtained from control subjects and was highly correlated with acetylation of sulfamethoxazole in vivo ( r > 0.80). The apparent V max for cystic fibrosis lymphocyte lysate was significantly ( p < 0.05) greater than that obtained for control lymphocyte lysate (72.99 ± 9.07 versus 60.97 ± 2.26 pmol/mg protein/min), and the apparent K m was significantly ( p < 0.05) lower (0.51 ± 0.07 versus 0.73 ± 0.06 mmol/L). Conclusion Blood cells may be used as surrogate markers to elucidate the mechanism (s) by which acetylation of sulfamethoxazole (catalyzed by the monomorphic N ‐acetyltransferase) is enhanced in subjects with cystic fibrosis. Both activation or activation and induction of the monomorphic N ‐acetyltransferase should be considered as possible mechanism(s) to explain this phenomenon. Clinical Pharmacology and Therapeutics (1994) 55, 427–433; doi: 10.1038/clpt.1994.52