| Abstract
| - Arsenic has been used successfully in clinical trials for treating acute promyelocytic leukemia(APL). Although sublethal doses of inorganic arsenic are used, little is known about thepharmacokinetics and metabolism of the high levels of arsenic in APL patients. To fill thisimportant gap, this study describes the speciation of arsenic in urine from four APL patientstreated with arsenic. Each patient was injected daily with an arsenite (AsIII) solution thatcontained 10 mg of As2O3 precursor. Speciation analysis of the patient urine samples collectedconsecutively for 48 h, encompassing two intravenous injections of arsenic, revealed the presenceof monomethylarsonous acid (MMAIII), dimethylarsinous acid (DMAIII), monomethylarsonicacid (MMAV), and dimethylarsinic acid (DMAV). The intermediate methyl arsenic metabolites,MMAIII and DMAIII, were detected in most urine samples from all of the patients when apreservative, diethyldithiocarbomate, was added to the urine samples to stabilize these trivalentarsenic species. The major arsenic species detected in the urine samples from the patientswere AsIII, MMAV, and DMAV, accounting for >95% of the total arsenic excreted. The relativeproportions of AsIII, AsV, MMAV, and DMAV in urine samples collected 24 h after the injectionsof AsIII were 27.6 ± 6.1, 2.8 ± 2.0, 22.8 ± 8.1, and 43.7 ± 13.3%, respectively. The relativelylower fraction of the methylated arsenic species in these APL patients under arsenic treatmentas compared with that from the general population exposed to much lower levels of arsenicsuggests that the high levels of AsIII inhibit the methylation of arsenic (inhibits the formationof methyl arsenic metabolites). The arsenic species excreted into the urine accounted for 32−65% of the total arsenic injected. These results suggest that other pathways of excretion, suchas through the bile, may play an important role in eliminating (removing) arsenic from thehuman body when challenged by high levels of AsIII.
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