PHA First Exam Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

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1 PHA 527 Firs Exm Fll 20 On my honor, I hv nihr givn nor rcivd unuhorizd id in doing his ssignmn. Nm Qusion S/Poins I. 30 ps II. III. IV 20 ps 5 ps 5 ps V. 25 ps VI. VII. VIII. IX. 0 ps 0 ps 0 ps 35 ps OAL: 70 ps Equions/Usful_phrmcoinic_qu_527

2 Qusion S I (ru or Fls) (30 poins) ru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls. Assum pssiv diffusion s h driving forc for disribuion. : F Assum firs ordr bsorpion procss. h r of bsorpion of his drug cross GI mmbrns will dpnd on h dos givn. 2: F A hydrophilic drug cnno hv volum of disribuion h is smllr hn Vp. 3: F A drug h shows zro ordr inics whn givn dos of 0 mg bid will coninu o show his highr doss. 4: F wo drugs show h sm /2. hy will show h sm l nd volum of disribuion. 5: F Whn h sm singl dos of h drug is givn orlly ihr s soluion or in form of slow rls formulion, h AU sims for boh h formulions r h sm. Hnc, h dosing rgimn should b sm for boh formulions. 6: F Plsm cn b prprd by rmoving 2+ from h blood. Equions/Usful_phrmcoinic_qu_527 2

3 Qusion S II (20 poins) ru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls. ru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls. A glucocoricoid is givn ovr long im s n IV infusion o rs. Undr hs condiions drug concnrions r consn fr bou hour. oncnrions fr 4 nd 8 hours r hus h sm in h blood. Prson X drmins fr 8 hours how mny glucocoricoid rcpors r occupid in idny, h livr nd h brin. h numbr of rcpors in hs hr issus is bou h sm nd h ffiniy of h glucocoricoid o h rcpors in h hr issus is idnicl. Whil h sm numbr of rcpors is occupid in idny nd livr fr 8 hours, much fwr rcpors r occupid in h brin h sm im. Which of h following smns r consisn (ru) or no consisn (Fls) wih his obsrvion? 7: F Glucocoricoids inrc wih rnsporrs in h brin h pump h drug ino h brin clls whil his is no h cs for idny nd livr 8: F h blood flow hrough h brin is lowr hn h hrough h idny nd livr. 9: F Proin binding in livr nd idny is mor pronouncd, hn in h brin, xplining h highr drug concnrions bl o inrc wih h rcpors in idny nd livr. 0: F h brin migh mboliz his glucocoricoid fficinly. Equions/Usful_phrmcoinic_qu_527 3

4 Qusion S III (5 poins) Lisd in h bl r hr propris of cidic drug molculs: RUG h frcion ionizd ph=7.4 nd h priion cofficin of h unionizd form. Frcion Unionizd ph=7.4 Priion officin of Unionizd form Molculr Wigh (lon) Ohr propris , Vry High ffiniy o pgp : Slc h corrc rn ordr wih which drugs -4 will b vilbl o h brin. A: slowr hn 2 slowr hn 3 slowr hn 4 B: slowr hn 3 slowr hn 2 slowr hn 4 : 4 slowr hn 2 slowr hn 3 slowr hn : 4 slowr hn 2 slowr hn slowr hn 3 E: Non of h bov smns rprsns h corrc nswr Equions/Usful_phrmcoinic_qu_527 4

5 Qusion S IV (ru or Fls) (5 poins) ru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls. Assum no civ rnspor. Assum wo unionizd, hydrophilic low molculr wigh drugs. 2: F omprd o f, h livr is lily o hv highr r of up for such drugs du o is highr blood flow r. 3: F Assum h sm fu for h wo drugs. h drug wih h highr issu binding will nr h issu fsr. 4: F Assum h sm fu for h wo drugs. h drug wih h highr plsm proin binding will nr h issu fsr. Equions/Usful_phrmcoinic_qu_527 5

6 onc. (ng/ml) onc. (ng/ml) Qusion S V (ru or Fls) (25 poins) im (h) im (h) rug A rug B ru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls 5: F rug A s r of liminion is no ffcd by h moun of drug in h body. 6: F rug A s liminion r consn hs h uni /ml. 7: F For rug A nd B, h frcion of drug limind pr hour is consn. 8: F rug A is only limind hrough rnsporrs in h idny. No mbolism occurs. rug A s concnrion-im profil migh loo vry similr o h of rug B, whn givn much lowr doss. 9: F hr is no on /2 for drug B. Equions/Usful_phrmcoinic_qu_527 6

7 Qusion S VI (0 poins) 20: h drug concnrions fr iv bolus injcion of drug wih firs ordr liminion (on comprmn body modl) ws 2ng/ml fr hour nd 0.8 ng/ml fr 3.5 hours pos injcion. Wh is h hlf-lif of his drug? A B E.44 h.89 h 4.36 h 0.37 h Non of h bov 2: A drug hs hlf-lif of 3hours. A dos of 2000 μg ws givn s n iv bolus injcion. Vd is 00L. hr hours pos injcion (ssum on comprmn body modl, firs ordr liminion), h concnrion ws 5 µg/l. Wh is h AU 0-? A B E 5 µg*h/l 86.5 µg*h/l 60.0 µg*h/l 90.0 µg*h/l Non of h bov Equions/Usful_phrmcoinic_qu_527 7

8 Qusion S VII (0 poins) 22: How will h incrs in boh issu binding nd livr blood flow ffc h iniil concnrion ( 0 ), clrnc (L), AU, nd hlf-lif ( /2 ) of drug A. Assum E is consn. A: 0, L, AU B: 0, L, AU : 0, L, AU : 0, L, AU E: non of bov combinions. Equions/Usful_phrmcoinic_qu_527 8

9 Qusion S VIII (0 poins) 23: hronic livr diss cuss 20% dcrs in vrpmil clrnc. Howvr, hlf-lif of vrpmil incrss 4 fold. lrly h volum of disribuion hs lso chngd du o h chronic livr diss. Wh is h volum of disribuion of vrpmil in pin wih chronic livr diss? (Hlhy populion vlus: L= 60L/h; Vd= 300 L) A: 300L B: 200L : 960L : 240L E: Non of bov Equions/Usful_phrmcoinic_qu_527 9

10 Qusion S IX (35 poins) 24: F Fr drug concnrions r lwys h sm in plsm nd issus, whn h disribuion occurs insnnously. 25: F Enzym inducion cn rsul in fsr ons of cion whn prodrug is mbolizd by his nzym, ssuming h prodrug is givn by iv bolus. 26: F rugs h r subjc o pgp rnspor in h GI mmbrns, migh show highr orl biovilbiliy whn givn wih drug h blocs pgp civiy. 27: F Giving drug in h form of slow dissolving sl migh llow lss frqun dosing. 28: F A slowr bsorpion migh b dvngous for drug wih nrrow hrpuic window. 29: F /AU=L s L=*Vd nd /AU=*Vd nd Vd=(/AU*), AU dpnds on. 30: F PK is imporn s doubling of h plsm concnrions will gnrlly rsul in doubling of h ffc. Equions/Usful_phrmcoinic_qu_527 0

11 Symbols = dos = dosing inrvl L = clrnc Vd = volum of disribuion = liminion r consn = bsorpion r consn F = frcion bsorbd (biovilbiliy) K 0 = infusion r = durion of infusion = plsm concnrion Gnrl Eliminion r consn ln L 2 ln Vd Hlf-lif / 2 Usful Phrmcoinic Equions ln Vd ln( 2) L Inrvnous bolus Iniil concnrion 0 Vd Plsm concnrion (singl dos) 0 Plsm concnrion (mulipl dos) 0 P (mulipl dos) 0 mx min 0 Avrg concnrion (sdy s) p ss L Orl dminisrion Plsm concnrion (singl dos) F Vd im of mximum concnrion (singl dos) ln mx Plsm concnrion (mulipl dos) F Vd im of mximum concnrion (mulipl dos) ln mx Avrg concnrion (sdy s) F L lrnc l os F AU l V d rough (mulipl dos) Equions/Usful_phrmcoinic_qu_527

12 onsn r infusion Plsm concnrion (during infusion) 0 L Plsm concnrion (sdy s) 0 L lculd clrnc (hiou quion) L Shor-rm infusion P (singl dos) L mx( ) rough (singl dos) Vd min( ) mx( ) P (mulipl dos) mx L rough (mulipl dos) min mx lculd liminion r consn ln mx min wih mx * = msurd p nd min * = msurd rough, msurd ovr h im inrvl lculd p K for minoglycosids mx mx wih mx * = msurd p, msurd im * fr h nd of h infusion lculd rough min min wih min * = msurd rough, msurd im * bfor h sr of h nx infusion lculd volum of disribuion Vd [ mx ( min )] lculd rcommndd dosing inrvl ln mx( dsird ) min( dsird ) lculd rcommndd dos V mx( dsird ) wo-omprmn-body Modl b AU / b / Vd Vd Vc r ss rinin lrnc L L cr cr ( 40 g) wigh ( ml) 72 p cr ( 40 g) wigh ( fml) 85 p cr Wih wigh in g, g in yrs, crinin plsm conc. in mg/dl nd L cr in ml/min K = (rL) Equions/Usful_phrmcoinic_qu_527 2

13 Mbolic nd Rnl lrnc E H = lin fu b Q l fu H in b l H = E Q H = H QH lin fu Q l fu H in b b F H = Q H Q H l in fu b l rn = RBFE = GFR in in ou l rn = r of xcrion plsm concnrion R of scrion - R of rbsorpion l rn = fu GFR Plsm concnrion l rn = Urin flow urin concnrion Plsm concnrion Idl Body Wigh Ml IBW = 50 g g for ch inch ovr 5f in high Fml IBW = 45.5 g g for ch inch ovr 5f in high Obs ABW = IBW + 0.4*(BW-IBW) Volum of isribuion V V P V V P lrnc l os AU V V K P fu fu l V d Equions/Usful_phrmcoinic_qu_527 3

14 Nm: UFI#: For On omprmn Body Modl If h dosing involvs h us of I.V. bolus dminisrion: For singl I.V. bolus dminisrion: 0 V 0 For mulipl I.V. bolus dminisrion: n n( ) V p: = 0; sdy s n rough: = mx ss V ( ) min ss mx ss If h dosing involvs h us of I.V. infusion: For singl shor-rm I.V. infusion: Sinc = for mx mx min V mx ( ) For mulipl shor-rm I.V. infusion sdy s: mx V min mx ( ) 4

15 Nm: UFI#: 5 If h dosing involvs I.V. infusion (mor quions): V (mos gnrl q.) during infusion = so, V (during infusion) sdy s, -, 0 so, L V V pss 0 0 (sdy s) rmmbring 0 nd V L If h dosing involvs orl dminisrion: For singl orl dos: V F ln mx For mulipl orl doss: V F ln mx

16 Nm: UFI#: 6

17 Nm: UFI#: 7