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. w. im . auP0 3 E lou ar \ HASKERLoLsttLiafgomaNTeonpyisriosT'oSxicCooLamaeymt EucronARnooadI.NGNUESwTaRnIAKL, MDEEDILCAIWNAER.E 19711 CENTRAL RESEARGH AN OEVELOPMENT DEPARTMENT PERSONAL AND CONFIDENTIAL JP.OLYG.MERLOSPCRHOIDAUVCOTS DEPARTMENT PARKERSBURG ce: J5.. MA.l CErodrmdarney -- PPPPDD -- PPAARRKKSSBBGG TTAL.. sFocshtreernk -- PPEPDD -- PPAARRKKSSEBGG 3Pp.. uTwhisRtalineetson -- PPPPDD -- P-A5R6K2S5BG G. L. Kennedy "Ee_ H- Hiasx kell August 25, 1982 AR 226 16,22. C v AMMOa NIUMpPEe RFLUn ORCOs CTANiOATo E (Cn -8) T(eRfeltoenInntiWoronerfkeoefrresAn)cmemoI ntwioouumyloduPrerlJfikuleluyortoo29o,mcatka1en9c82as,teevelre(atClt-8e]rimiptnoorBtR.lanotoJ.d soZufigpgfeesl ttiioonns. inAwcoqrukiesristioins avnedryinitmeproprrteatnattiionnuonfdeCr-s8tanbdlionogd choownctehnetra hHuamsakenllbodcyo.rrhealndaltees toC-8theandhumhaonw saictcuuartaitoenl,y oTuro abentitmearl miondteelrspreatt these data, consider the following modifications: + TSohfreiaatc0ec.0u0mt6uolpacptamlilonbliwothoedannlei"tvaevlweoruailgsdetecberomnecmdeonrtearaa"tpripaortneo""dTShaveyesr agvthieevreasgaevetbrhalegoeopdlaotfleeav9ue1,l daooyrfs s0.tof0e0a6deym-ppslptomay/tmdeea,nyt.cxon9-1 cCeeleniptmrirenasatetiniotonsn.t(h0e.5d46ynappmmi)c tashpaetctmsoreof celxopsoesluyre and T(hVed) c"aelqcuuallattioontsheasbsluomoed acovmoplarutmmeenotf donilsytri(b5u.t5ion : liters). Since C-8 is water soluble and binds protein, the Vd would actually be closer to the v1oiltuemres/7o0f ktgotmaaln)b.ody water (approximately 42 3g S 000216 EIDOT2164 J. G. Loschiavo -2- August 25, 1982 eo Tion mtohreeboadcycuarsatweellylasassespsredtihectrebtleonotdiolnevoeflsC-8 afnotrimculiapsatecdomwmiotnhlycounstedinuteodesltoiwm-alteeveldruegx-potshuerrea,py regimen can be employed. Assumptions: - T(hsetebaldoyo-dstalteev)el,coCnpc,entirsataitona p(lia.te.e,au aeqbusaolr)p.tion and elimination approximately - Tthoetalvolbuomdey woaftedri,stroirbu4t2iolni,tervsd., is in - The daily dose (D/T) is 0.081 mg/day. - Tehsetimealtiemdinaftrioomnahallift-elriafteu,retre1p/2o,rtiosn obnuet iconudlidvidvuaarly. conThseidevraalbuley.is 655 days, Then from Goodman and Gilman (1970): c@ _fela$aecis2 3 - where f = fraction absorbed - solving for , f._TCHpeEvdreer s __0.Cie 5t4i6r4em2gsoer/edlaeners - then: t(d1a/ys2) 3 Absorbed 31507 61..5050 615050 366505 00..5350 5350 Tohnulsy, tdheaptengdrienagteronththaen a3c0%tuaolf tatm1o/2s,phweericcanC-8estiismate easbtsiomrabteed,. bTuhtisuntisiliwnegeknneorwaltheagraceteumaelnttwi1t/h2 ywoeurwill g abnostorbpetiaobnl.e to accurately calculate fractional < g EID072165 a 000237 J. G. Loschiavo -3- August 25, 1982 + RyoeugrardsiungggesttheisoenscainlcutlheatiJounlsy a29ndmeimnorraensdpuomn,se to - Msooruercehsu:man data is necessary from two 1. Ocfurrpelnatteaeumpl(osyteeeasdy-fsotratdee)tercmoinncaetnitornaZions 2. efaonmrdpldoteyhteeeesrumriinnnoaatrliyoonngeexrocfreetxtipheoonsbedlroatotedo. Ct-81/2 - taenalhyavseispoefrfotrhmeeddisrtardiiboucthiemoincaalndanedffebcitoscheofmicCa-8l. pisgl ee RTEISMEoATRHCYH BT)OXIPCAOSLTOOGRIST gg ) EID07216 a 000218