Characterization of the disposition of fostamatinib in Japanese subjects including pharmacokinetic assessment in dry blood spots: results from two phase I clinical studies.
Purpose: The aims of the present study were to characterize the pharmacokinetics of fostamatinib in two phase I studies in healthy Japanese subjects after single- and multiple-dose administration, and to evaluate the utility of dried blood spot (DBS) sampling. Methods: In study A, 40 Japanese and 16...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 72; no. 1; pp. 61 - 72 |
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| Autores principales: | , , , , |
| Formato: | research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Springer Nature
Jan2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=112083891&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 112083891 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Jan2016 vid: 72 iid: 1 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 112083891 112083891 112083891 10.1007/s00228-015-1961-5 112083891 ppf: 61 ppct: 11 formats: fmt: @attributes: type: P tig: atl: Characterization of the disposition of fostamatinib in Japanese subjects including pharmacokinetic assessment in dry blood spots: results from two phase I clinical studies. aug: au: Martin, Paul Cheung, S. Yen, Mark Han, David Gillen, Michael affil: AstraZeneca Pharmaceuticals, Alderley Park Macclesfield SK10 4TF UK sug: subj: Antiinflammatory Agents Pharmacokinetics Blood Chemical Analysis Human Male Female Japan Japanese Persons Antiinflammatory Agents Administration and Dosage Double-Blind Studies Randomized Controlled Trials White Persons Dose-Response Relationship Male Female ab: Purpose: The aims of the present study were to characterize the pharmacokinetics of fostamatinib in two phase I studies in healthy Japanese subjects after single- and multiple-dose administration, and to evaluate the utility of dried blood spot (DBS) sampling. Methods: In study A, 40 Japanese and 16 white subjects were randomized in a double-blind parallel group study consisting of seven cohorts, which received either placebo or a fostamatinib dose between 50 and 200 mg after single and multiple dosing. Pharmacokinetics of R406 (active metabolite of fostamatinib) in plasma and urine was assessed, and safety was intensively monitored. Study B was an open-label study that assessed fostamatinib 100 and 200 mg in 24 Japanese subjects. In addition to plasma and urine sampling (as for study A), pharmacokinetics was also assessed in blood. Results: Mean maximum plasma concentration ( C) and area under total plasma concentration-time curve (AUC) increased with increasing dose in Japanese subjects. Steady state was achieved in 5-7 days for all doses. C and AUC were both higher in Japanese subjects administered a 150-mg single dose than in white subjects. This difference was maintained for steady state exposure by day 10. Overall, R406 blood concentrations were consistent and ∼2.5-fold higher than in plasma. Minimal (<0.1 %) R406 was excreted in urine. Fostamatinib was well tolerated at all doses. Conclusions: Fostamatinib pharmacokinetics following single- and multiple-dose administration was approximately dose proportional at all doses ≤150 mg and greater than dose proportional at 200 mg in Japanese subjects. Japanese subjects administered fostamatinib 150 mg had higher exposure than white subjects. R406 could be measured in DBS samples and distributed into red blood cells, and DBS sampling was a useful method for assessing R406 pharmacokinetics. pubtype: Academic Journal doctype: research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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