a) The lowest white blood cell count and absolute neutrophil count were obviously substantially lower in patients who were fast acetylators. This indicates that acetylator status is a predisposing factor to the development of myelosuppression.
b) Obviously, the fast acetylators are at greatest risk, since these are the individuals who exhibit the greatest level of reduction in WBC and neutrophil counts.
c) Since fast acetylators are at increased risk for developing myelosuppression, it is obvious that the acetyl metabolite of amonafide must be the proximate species causing myelosuppression. If tumor killing activity resides in the same species as does myelosuppression, then acetylation of amonafide results in activation of the drug. Thus, doses in those individuals who form more of the active metabolite should be lower than those who form less of this species. Therefore, the dose of amonafide should be higher in slow acetylators than fast acetylators.
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