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Article: Systemic availability of arsenic from oral arsenic-trioxide used to treat patients with hematological malignancies

TitleSystemic availability of arsenic from oral arsenic-trioxide used to treat patients with hematological malignancies
Authors
KeywordsAcute leukemia
Arsenic trioxide
Oral bioavailability
Issue Date2002
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00228/index.htm
Citation
European Journal Of Clinical Pharmacology, 2002, v. 58 n. 8, p. 521-526 How to Cite?
AbstractAims: Arsenic trioxide (As2O3) is increasingly used to treat hematological malignancies. This involves daily intravenous (i.v.) administration for 4-8 weeks, with its attendant drawbacks: inconvenience, risks and expense of maintaining suitable vascular access and hospitalization. We therefore developed an oral formulation, administered it to patients and set out to assess the resulting systemic bioavailability of arsenic. Methods: With ethics committee approval, nine patients with refractory/relapsed acute myeloid leukemia were recruited after giving informed consent. On day 1, each received 10 mg As2O3 by i.v. infusion over 1 h. Each patient swallowed 10 mg As2O3 in 10 ml oral solution 24 h later (day 2) and on subsequent days thereafter. Prior to and until 48 h post-i.v. dosing, timed venous blood samples were drawn and corresponding plasma and whole blood arsenic concentrations were determined by atomic absorption spectroscopy. Systemic bioavailability was inferred from the area under the arsenic level versus time curve (AUC) using the trapezoidal rule. Day-1 AUC after i.v. dosing was taken to be 100% and that attributed to oral dosing (day 2) was then calculated. The 48-h arsenic levels in blood cells were calculated using hematocrit values and corresponding plasma and whole blood arsenic concentrations. Results: Respective day-2 mean plasma and blood AUCs attributed to oral dosing were 99% and 87% of corresponding day-1 values. On average, 48-h blood cell arsenic levels were 270% greater than in plasma (P = 0.013). No patient suffered unexpected complications, and five went into remission. Conclusions: Compared with i.v. dosing, our oral As2O3 formulation was more convenient and cost effective, and the ensuing systemic bioavailability of arsenic appeared similar. Arsenic seemed to be concentrated in the cellular fraction of blood 48 h after starting As2O3 treatment.
Persistent Identifierhttp://hdl.handle.net/10722/148287
ISSN
2015 Impact Factor: 2.71
2015 SCImago Journal Rankings: 1.096
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKumana, CRen_HK
dc.contributor.authorAu, WYen_HK
dc.contributor.authorLee, NSLen_HK
dc.contributor.authorKou, Men_HK
dc.contributor.authorMak, RWMen_HK
dc.contributor.authorLam, CWen_HK
dc.contributor.authorKwong, YLen_HK
dc.date.accessioned2012-05-29T06:12:00Z-
dc.date.available2012-05-29T06:12:00Z-
dc.date.issued2002en_HK
dc.identifier.citationEuropean Journal Of Clinical Pharmacology, 2002, v. 58 n. 8, p. 521-526en_HK
dc.identifier.issn0031-6970en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148287-
dc.description.abstractAims: Arsenic trioxide (As2O3) is increasingly used to treat hematological malignancies. This involves daily intravenous (i.v.) administration for 4-8 weeks, with its attendant drawbacks: inconvenience, risks and expense of maintaining suitable vascular access and hospitalization. We therefore developed an oral formulation, administered it to patients and set out to assess the resulting systemic bioavailability of arsenic. Methods: With ethics committee approval, nine patients with refractory/relapsed acute myeloid leukemia were recruited after giving informed consent. On day 1, each received 10 mg As2O3 by i.v. infusion over 1 h. Each patient swallowed 10 mg As2O3 in 10 ml oral solution 24 h later (day 2) and on subsequent days thereafter. Prior to and until 48 h post-i.v. dosing, timed venous blood samples were drawn and corresponding plasma and whole blood arsenic concentrations were determined by atomic absorption spectroscopy. Systemic bioavailability was inferred from the area under the arsenic level versus time curve (AUC) using the trapezoidal rule. Day-1 AUC after i.v. dosing was taken to be 100% and that attributed to oral dosing (day 2) was then calculated. The 48-h arsenic levels in blood cells were calculated using hematocrit values and corresponding plasma and whole blood arsenic concentrations. Results: Respective day-2 mean plasma and blood AUCs attributed to oral dosing were 99% and 87% of corresponding day-1 values. On average, 48-h blood cell arsenic levels were 270% greater than in plasma (P = 0.013). No patient suffered unexpected complications, and five went into remission. Conclusions: Compared with i.v. dosing, our oral As2O3 formulation was more convenient and cost effective, and the ensuing systemic bioavailability of arsenic appeared similar. Arsenic seemed to be concentrated in the cellular fraction of blood 48 h after starting As2O3 treatment.en_HK
dc.languageengen_US
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00228/index.htmen_HK
dc.relation.ispartofEuropean Journal of Clinical Pharmacologyen_HK
dc.subjectAcute leukemiaen_HK
dc.subjectArsenic trioxideen_HK
dc.subjectOral bioavailabilityen_HK
dc.subject.meshAcute Diseaseen_US
dc.subject.meshAdministration, Oralen_US
dc.subject.meshAdolescenten_US
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAntineoplastic Agents - Administration & Dosage - Blood - Therapeutic Useen_US
dc.subject.meshArea Under Curveen_US
dc.subject.meshArsenicals - Administration & Dosage - Blood - Therapeutic Useen_US
dc.subject.meshBiological Availabilityen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshInfusions, Intravenousen_US
dc.subject.meshLeukemia, Myeloid - Blood - Drug Therapyen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshOxides - Administration & Dosage - Blood - Therapeutic Useen_US
dc.subject.meshTime Factorsen_US
dc.titleSystemic availability of arsenic from oral arsenic-trioxide used to treat patients with hematological malignanciesen_HK
dc.typeArticleen_HK
dc.identifier.emailLam, CW:ching-wanlam@pathology.hku.hken_HK
dc.identifier.emailKwong, YL:ylkwong@hku.hken_HK
dc.identifier.authorityLam, CW=rp00260en_HK
dc.identifier.authorityKwong, YL=rp00358en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1007/s00228-002-0514-xen_HK
dc.identifier.pmid12451429-
dc.identifier.scopuseid_2-s2.0-0036451137en_HK
dc.identifier.hkuros81126-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036451137&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume58en_HK
dc.identifier.issue8en_HK
dc.identifier.spage521en_HK
dc.identifier.epage526en_HK
dc.identifier.isiWOS:000179833800005-
dc.publisher.placeGermanyen_HK
dc.identifier.scopusauthoridKumana, CR=7005112381en_HK
dc.identifier.scopusauthoridAu, WY=7202383089en_HK
dc.identifier.scopusauthoridLee, NSL=27168657300en_HK
dc.identifier.scopusauthoridKou, M=7004545950en_HK
dc.identifier.scopusauthoridMak, RWM=7004972794en_HK
dc.identifier.scopusauthoridLam, CW=34570692600en_HK
dc.identifier.scopusauthoridKwong, YL=7102818954en_HK

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