INFUS! (NTRAVENA - > Sait Kitts | €g anhbiotixa , elextrolit , ~ Bo Mudah diafur / constant input rate ~ Flustuasi (-) + undet:s terapi cempit > 2ere onder peease ¢ | setuvated Cplerteau) tnancarhall 3 ohn. makanon Cone he Mass balance , bi MB yf de ae 7 Kec e = Be (1g kat) Steady state Bs Re = CC, Ose tau: 2°" wo Rafe in = Rate cut hae Bo AQ =Va.KR a Re Va KK. Coe eeal we Copies Kaa OS") Inth = 05 Cy Lath, = O75 Css Sth = O8F5 Ces 3a xth = 03 Cs 4xth = 0.9395 Cos a 95% 66xth = 0.99 Cy 2 Bb x a = 90-95 Te Cas Procosnomde, LD = 1.0 gram MD = 0.5 gram C= chOAM AG Ose (40) to reach Cog immeciatety - by tv bolus, felowed by infusion to mamtain target cone . assume : t cm a ufus:lLD = Vics Cat time zero) or Ro © superposcbian principle” K «Ws LD 2 v.C5¢ = * ora: FLD = V.Gy + UDe = “Tune course : « w bolus : Cootug = Cos. apne « w unfoson: Cing = Ces Co — 97 Ket) Ce Coos + Cine = Coe o eee! cea A i erat ot.) ot a Decline in Concentration afar mfosion ceases Vis-cc + fe 2 - Sic me bgt CGCom Gis max € ofter WV bolus —CKet & after last’ ah ter last) asb,cd ¢ different LD) as b E d: LD OD Cop Ve LO = Co Va LO & Cy.Va {p=0a PENGATURAN DOSIS GANDA (MULTIPLE DOSAGE REGIMENS) \ Empurical approach amilihan dosis, frekvens? (intervat) pemberian — clinical Jadgement imitertions = + suo therapeutic Level «toxic (evel x Slow process » +h ufic response « Varlability different tesponse 2 (Kmetic approach 4 si advantages : more rapid — drug concentration Methods : A. Clearance method - Furst choice —» semple ~ baste approach : average conc fluctuation eg. antibaxteri , kordiotonika , antikonvulsan , hormon Cone* Lu. infusion + pate ms rate cut Ro = Cl. Ces = Oval + average rate m = average rafe out D0. + B= ees average alinnation rate e9.® D2 ago Fa( | tent m T= aah J “hy® Theophylline : C2 = 72 “min = 0.072 Yanin v = 34L eae Therapeutic range (bronchodilator effect ): 5-20 PE Sont Aim for Css = 13 ae = = ae = OTD = 0.94 MZ,» 1350 8/0, Wv Oral T th) O cma) FY HH. Issues: “4 4 350 40 - patient Compliance 2 os 20 = Pi issue (fluctuation & 2 40 a accumutaton ) © 340 10 Fal Ve 340 Large T requires Large D T+ 24h, tah + FOX, > range - Unsuctable Ts Bh, Cmax = 13+ '& C19) 2195 mg, Coin = 13 ~ Me (13) © 65 ™B/_ C+ 6h Cmax = (3+ Ye C10) 218 ™B/_ Cum = 132 Cro) 2 B omg 4 wo Es Gh, D= 240mg Cg = Gp iv = Cop oval fuuctuation iv A oralSound off theophylline 200 mg 1 425 mg. Choose (1 ¥200 mg) + (125 mg) = 325 mq So mg D= 325 mg, (2 340 my) ‘ Zs 6h Bee. & Dp, it = IS apy ! Betas pag Mae 956 HBL, . Adwstment to extrting egimens Change ‘Wm Clearance ~ normal case . FR = og @ 2 - diseace .: FO" CL C2". Coe ce Se ee We ce = “2 = (Can choose ;@ Dz Dd 4 calculate new T* @ TT > calculate new D* Continued oral therapy following “iy infustor 3 FPR Css = Coe Ro = C0. re Dip De Re Re ( g- an ct FRB +ag Life Method, asic approach Css,max % Ces, min tot NN i A = V.C = Ags max = V.Css,max arom Ass min = V. Cos. min | Ass, max : 4 | \ Ass.nax = Assmin + D (begining the interval ) a \ Asseotin = Assimax. @ MLE (during the interval) x ca Assemen , Ss. men (<1) Ass, min es, Max Css, max. cag Ket ce Se In Cr)Acs,max = Ass,win + D = 1. Ass,max + D—> De CI-r) Ass, max D A Ass max® awe Ass,nin = DOSAGE IZEGIMENS 1. Therapeutic ange ( amourct ) usa v. MSC MEA Vv. MEC 2. Ags.max << MSA Ass, min = > MEA - Assumin Ass, max non a A. T= 1 in(L) round off (Ts 6,8, 1a,24h) calculate raw a ae 3) FE y LR, > aie 5% De (1-7) Ass, max oral dore = FD» Ds (i-r) Ames G. Round off D to available value 7. Cheds Calculafian with rended values 2D &D Ass,max = ey Ass, min = 1. Ass, max . , t Assimax Dor Acsinae ~ CFD) “4. Ttheophyline 2:72 Whim, Vi BAL, Fat Ka. 0 2 013h', tye M20) » Sah Treurapertic rage = 5-20 fg), Aum Fer = Css.max = 18 £4/,, > Ass, max = G12 mg TS ae ee =aAss. min aso ue Too «= — = ge s¢ Ass, max ed { = lel Zia w(t) = Sa Inconvenient + Choose z. Gh, new rz @ SF FD = Ct-T) Ass, max ED = O54 x 6a = 330 mg (=D) = 0,46 Awatlable doses ao, 1a8, SO mg , Choose 325 + ACO + 125 check « 2 22. BE. Ass, max ar see G02 ng > Css, max S79, Ass, mtn = 1. Ags.max = Ass,max - FD = 277 "4 = Css, max = 277 = f 34 BAS Mtg Regimen : T=t Km U) flwetuatien wrth 4% is very common (ii) D juse suffectert for effect cali) LOC?) <« 2D 7 4: 65 =e = RED 5 Ascmn = FD > MEA flveruation between FD and 2 FD ow MSA ~ MEA = FD ronttertions Ass, max 1) Floctvation x 2 Caf: thenapectte range) eg. 9-lo Mass difReult to achieve e4. 6-10 P3/me. if mms €, maxeia » 1013 /ug Ctoxic ) Max= 40, min F< 6 Hine (Sub therapeutic ) W) Incenveniert for Long t¥a £4 tn digitoxin & 6 days tK Chloroguin 2 ¢ month Inconventent for short th 29 tH Pen-G 2th > ath? aN a a aEvaluation of repeated exposure , 24. secticides Tz 0 Ket Ass. max ~ 2. 5) Wdiceteas = ne ir Cur) <1 > Ass.nex > &D 24.@ Coffeme = t% 3 teach Ze tah Kee ©, 693/46, = 0,199 h7! rs gr Kez = 0,0929 > Ass max * PD (1 = 0,0929 = D 46,9071 Assimax =U FD , because To 3-4 x tK NO serious problem for accumulation “ME E44 -» degree of accumulation is small fluctuation i¢ large o ©) Tetrahydrocannalinal (THC) tKheu3 4 Sin ud Ket 288 asa ra erke® wos Ags. max = ae. SF) \-7 Ass.mn 2 0,8 Ass,max = 4PD Serious preblem for accumulation fF T Kt + dogree of accumulate is large fsetuation cs Smad © Phenobarbital — hypnotic T + 24h 4% = 24 - 140h “ ” £olerance Ass.nex 41 9FD Ass.mn «1 REDApproach to steady state s S to0e 5 3 E.g00 ae 7 & wv. bolus Dore number (n> Time after dosing Ass. max \ ot D 2 t+ TD +d 3 act PptrD+ dD : i i n (n-tt reper Da trDe D os Bes max 9 Ddcerenre-.. +rn') vorh a) dC ae 3 or FD SS £4, Da lo mg 1 72 0,6 Dose number Cn) Ah,max (mg) An, min (mq) ‘ {oo aa +00 a é exe we 2102 36 3 '96 OG nid # 276 (30,6 5 2306 (38,4 i * 250 150