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

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1 Nm: PHA 5127 Finl Exm Fll 2011 On my honor, I hv nihr givn nor rcivd unuhorizd id in doing his ssignmn. Nm: Pls rnsfr h nswrs ono h bubbl sh. Th qusion numbr rfrs o h numbr on h bubbl sh. Pls fill in ll h informion ncssry o idnify yourslf. Th procors will lso collc your xms. Good LUK. Qusion/ ---Poins TOTAL 134_/ps 1

2 Nm: Qusion s I (10 ps): A drug hs bn formuld s cpsul wih ru zro ordr rls inics. Th drug conn pr cpsul is 100 mg. Th rls r is 20 mg/hr. Rls of h drug from h cpsul is h r limiing sp for bsorpion. Orl biovilbiliy is 100%. Th hlf-lif of h drug is 1 hours. Th pin rcivs on cpsul vry 8 hours. Th flucuion for his drug should b lss hn 3. Slc whhr h following smns r Tru (A) or Fls (B). 1: T F By looing jus h plsm concnrion im profils, on cn no m h dcision whhr h drug ws givn orlly wih bov formulion or s iv. Injcion. 2: T F By looing jus h plsm concnrion im profils, on cn no m h dcision whhr h drug ws givn orlly wih bov formulion or s i.v. Infusion. 3: T F Assuming h h hlf-lif of h drug is 1 hours, drug concnrions fr 4 nd 5 hours will b vry similr. 4: T F If givn vry 8 hours, sdy s will b obsrvd lrdy for h scond dos. 5: T F Th flucuion for his drug should b smllr hn 3. osing vry 8 hours will b oy. 2

3 Nm: Qusion s II (6 ps): Slc from h following smns whhr h smns r Tru (A) or Fls (B). Assum rug A is fully convrd ino is Mboli B. Boh r full goniss nd show h sm rcpor ffiniy. V d nd issu nd plsm proin binding r idnicl. Howvr, Mboli B hs ol clrnc 10 ims lrgr hn h of rug A. Assum drug A is givn s n iv bolus injcion. 6: T F Mboli B s rminl slop will b spr whn plod on smilog ppr hn h of h prn, drug A. 7: T F Mboli B nd prn drug A will b qully conribuing o h phrmcologicl ffc. 8: T F of h prn drug will b idnicl o h r consn wih which Mboli B will b formd. 3

4 Nm: Qusion s III (4 ps): Slc from h following smns whhr h smns r Tru (A) or Fls (B). Assum mulipl dosing siuion. 9: T F For lipophilic drug h is clrd hrough mbolism (low xrcion drug) nd for which f u =f ut (vn if f u chngs) on cn s: Th srongr h issu nd plsm proin binding h mor pronouncd h dgr of ccumulion. 10: T F For lipophilic drug h is clrd hrough mbolism (low xrcion drug) nd for which f u =f ut (vn if f u chngs) on cn s: Th srongr h issu nd plsm proin binding h smllr h flucuion bwn p nd rough concnrion. 4

5 Nm: Qusion s IV (20 ps): Th following pplis o qusions 11-14: A 60-g pin is o b srd on coninuous inrvnous infusion (h pump will coninuously wor, no mulipl shor rm infusions). From prvious rgimn of h sm drug, you sim h pin s is 0.07 h -1 nd h V d is 40 L. rug from prvious dos is rmining in h body of h pin. This drug concnrion is 10 mg/l dircly bfor h sr of h consn r infusion. Qusion 11: Wh r of infusion ( 0 for h following consn r infusion) should rsul in sdy s drug concnrion of p ss of 20 mg/l. Round pproprily. (5 ps) A: 56 mg/ 0.5 hours B: 56 mg/ 1 hours : 28 mg/hr : 28 mg E: non of h bov 5

6 Nm: Th following pplis o qusions 11-14: A 60-g pin is o b srd on coninuous inrvnous infusion (h pump will coninuously wor, NOT mulipl shor rm infusions). From prvious rgimn of h sm drug, you sim h pin s is 0.07 h -1 nd h V d is 40 L. rug from prvious dos is rmining in h body of h pin. This drug concnrion is 10 mg/l dircly bfor h sr of h consn r infusion. Qusion 12: If h p ss is o b 20 mg/l, wh should b h loding dos (mg) givn s inrvnous bolus injcion. Rmmbr h drug concnrion bfor h sr of h infusion ws 10 mg/l. Round pproprily. (5 ps) A: 400 mg B: 800 mg : 1200 mg : 1220 mg E: non of h bov 6

7 Nm: Th following pplis o qusions 11-14: A 60-g pin is o b srd on coninuous inrvnous infusion (h pump will coninuously wor, NOT mulipl shor rm infusions). From prvious rgimn of h sm drug, you sim h pin s is 0.07 h -1 nd h V d is 40 L. rug from prvious dos is rmining in h body of h pin. This drug concnrion is 10 mg/l dircly bfor h sr of h consn r infusion. Qusion 13: Wh will b h plsm concnrion 1 hour fr sr of h coninuous infusion (rmmbr loding dos ws givn). Round pproprily. (5 ps) A: 3.9 mg/l B: 4.0 mg/l : 30 mg/l : 20 mg/l E: Non of h bov. 7

8 Nm: Th following pplis o qusions 11-14: A 60-g pin is o b srd on coninuous inrvnous infusion (h pump will coninuously wor, NOT mulipl shor rm infusions). From prvious rgimn of h sm drug, you sim h pin s is 0.07 h -1 nd h V d is 40 L. rug from prvious dos is rmining in h body of h pin. This drug concnrion is 10 mg/l dircly bfor h sr of h consn r infusion. Qusion 14: Th infusion is coninud for 3 dys nd h sdy s concnrion hs bn minind 20 mg/l. Th physicin wns o chng h drug dlivry o mulipl shor rm infusions wih mx of 20 mg/l nd rough of 10mg/L. (Hin: Th firs shor-rm infusions should b dminisrd whn h rmining plsm concnrion rchs 10 mg/l). How mny hours fr h coninuous infusion hs bn soppd should h firs shor-rm infusion b givn. Round pproprily. (5 poins) A: 1 h B: 2 h : 8 h : 10 h E: Non of h bov. 8

9 Nm: Qusion s V (10 poins) Qusion 15: A 59 yr old whi ml, pin is hospilizd for GI surgry. Bfor surgry you r sd o sr h pin on gnmycin (n minoglycosid; Vd=0.25 L/g). Addiionl pin d r High 5 f, 1 in Wigh: 52 g Srum crinin: 1.3 mg/dl Vd=0.25 L/g Provid n ppropri gnmycin minnnc dosing rgimn (u nd os/dosing inrvl), ssuming n infusion im of 1 hour. Assum dsird p of 6 mg/l nd rough of 1 mg/l. Round pproprily. (10 poins) You slcd u of: A: 6 hours B: 12 hours : 13 hours : 23 hours E: 24 hours Qusion 16. You slcd os of: A: 50 mg pr dosing inrvl B: 60 mg pr dosing inrvl : 70 mg pr dosing inrvl : 80 mg pr dosing inrvl E: Non of h bov. 9

10 Nm: Qusion s VI (5 poins) coninuion of qusion s V Qusion 17: lcul loding dos (givn s n 1 hour infusion) for h prvious siuion. A: 40 mg B: 60 mg : 70 mg : 80 mg E: Non of h bov. 10

11 Nm: Qusion s VII coninuion of qusion s V nd VI (9 poins) P nd rough concnrions wr drmind round h fourh dos. Us h u you hv clculd if ncssry. A 7:55 m rough ws n o b 0.4 mg/l; 8-9 m infusion of h drug; 9 m p ws n o b 4.6 mg/l. (9 poins) 18: T F Trough smpls r lwys n bfor p smpls. 19: T F Trough smpls wr n bfor p smpls s sdy s ws no y rchd. 20: T F To clcul for h pin on hs o divid ln (4.6/0.4) by h im h pssd from 7:55 m o 9:00 m, nmly 65 minus (bou 1 hr) 11

12 Nm: Qusion s VIII (10 ps) onsidr h following quion: Slc h ru smns concrning h following pr of h quion: (10 poins) 21: T F This pr provids informion on how much h firs mx (fr h firs shor rm infusion) is wy from h sdy lvl of coninuous infusion using h sm o. 22: T F This pr llows h clculion of h rough concnrion fr h sop of h infusion, s i convrs h p lvls ino h rough vlu 23: T F This pr ms sur h h clculd plsm concnrions will incrs wih incrsing infusion im. 24: T F This xprssion will b numbr bwn 0 nd 1. 25: T F This pr of h quion will b idnicl for givn drug indpndn on whhr h drug is givn s mulipl bolus injcion or mulipl shor im infusion s long s h dosing inrvl is h sm for boh forms of dminisrion. 12

13 Nm: Qusion s IX (8 ps) onsidr h following rlionship. 26: T F This quion cn b usd for mulipl shor rm infusions if is s o 0 27: T F F= p / rough 28: T F This rlionship cn b usd o clcul h dosing inrvl for mulipl shor-rm infusions if on dds h infusion im o h bov xprssion. 29: T F L s ssum =0. Using his quion for h clculion of h dosing inrvl of orl dosg forms is sf, s h flucuion will b lss hn ssumd during hs clculions. 13

14 Nm: Qusion S X (15 poins) Qusion 30-34: Two pins rcivd drug, which is only clrd by h livr, s n iv bolus injcion. Phrmcoinic nd physiologicl chrcrisics, such s dos, frcion of h drug unbound in plsm (fu), volum of plsm (Vp) nd volum of h issu wr (VTW) in boh pins r shown blow. Assum h boh pins show h sm issu proin binding. TABLE 1: INPUT PARAMETERS Pin 1 Pin 2 [mg] Lin fu Vp [L] 3 3 VTW [L] Indic which of h following prmrs (qusions 27-31) in pin 2 will b clrly lrgr (A), b ABOUT h sm (B), or will b clrly smllr () hn hos in Pin 1. Tbl 2: OUTPUT PARAMETERS Qusion: 30. (3 poins) Vd [L] of Pin 2 Lrgr (A), sm (B), Smllr () hn in Pin (3 poins) L [L/h] of Pin 2 Lrgr (A), sm (B), Smllr () hn in Pin (3 poins) 1/2 [h] of Pin 2 Lrgr (A), sm (B), Smllr () hn in Pin (3 poins) P [µg/ml] of Pin 2 Lrgr (A), sm (B), Smllr () hn in Pin (3 poins) AU [µg/ml*h] of Pin 2 Lrgr (A), sm (B), Smllr () hn in Pin 1 14

15 Nm: Qusion S XI (6 poins) Qusion 35: Th following concnrion im profils wr obsrvd fr mulipl iv bolus injcions of drug. Th wo curvs diffr in on of h inpu prmrs (os, u, L or Vd). 100 INPUT OUTPUT 100 [mg] P(ss) u [h] Trough(ss) n r(ss) L pv(ss) Vd [1/h] Fluc. [%] F This lin blongs o h missing inpu d This lin blongs o h missing inpu d Idnify h on inpu prmr h diffrs (qusion 32) A: os B: lrnc : Volum of disribuion : u E: non of h bov 15

16 Nm: Qusion S XII (10 ps) Qusion 36: Which of h following fcors significnly migh ffc h rnl clrnc of mhmphmin: 1. plsm proin binding 2. Urin flow 3. Tissu proin binding 4. ph of urin 5. GFR A: 1, 2, 4, 5 B: 1, 2, 4 : 1, 5 : 1, 3, 4, 5 E: ll of h bov combinions 16

17 Nm: Qusion S XIII (12 poins) Qusions Assum firs-ordr procsss. Mr whhr h following smns r ru (A) or fls (B). 37: T F For wo comprmn modl drug, 10 is smllr hn b. 38: T F M Assum h drug is mbolizd. Th K of h mboli is 20 h -1 whil h of h prn drug is h -1. If h plsm concnrions 10 hours fr injcion of h prn drug r 1 µg/ml for h prn drug nd 0.5 µg/ml for h mboli, h plsm concnrions 13 hours fr injcion of h prn drug mus b 0.5 µg/ml for h prn drug nd 0.25µg/ml for h mboli. (Assum firs-ordr inics for ll liminion procsss.) 39: T F For wo-comprmn modl drug, h volum of disribuion jus fr dminisrion of h drug is lrgr hn h obsrvd som im lr. 40: T F lrnc nd volum of disribuion r lwys indpndn prmrs. 17

18 Nm: Qusion S XIV Qusions (9 poins) Slc h mos ppropri diffrnil quion for h following siuions. A givn diffrnil quion migh hv o b usd mor hn onc. Assum X is h moun of drug in h body (drug h hs bn bsorbd nd hs no y bn limind) nd A is h moun lf h bsorpion si. A: dx/d= - B: dx/d= - - *X : dx/d= - *A + *X : dx/d= - *X E: non of h bov 41: A drug h is bsorbd nd limind hrough civ rnspor. Boh rnsporr sysms r surd (Slc from A-E) 42: An immdi rls bl of drug bl o cross mmbrns sily nd limind hrough rnl filrion. (Slc from A-E) 43: A high xrcion drug givn s n iv bolus injcion showing linr phrmcoinics (Slc from A-E) 18

19 Symbols Usful Phrmcoinic Equions = dos = dosing inrvl L = clrnc Vd = volum of disribuion = liminion r consn = bsorpion r consn F = frcion bsorbd (biovilbiliy) K 0 = infusion r T = durion of infusion = plsm concnrion Gnrl Eliminion r consn 1 ln L Vd 2 ln ln Hlf-lif Vd ln( 2) / L Inrvnous bolus Trough (mulipl dos) 0 min 1 Avrg concnrion (sdy s) pss L Orl dminisrion Plsm concnrion (singl dos) F Vd Tim of mximum concnrion (singl dos) ln mx Plsm concnrion (mulipl dos) F Vd 1 1 Iniil concnrion 0 Vd Plsm concnrion (singl dos) 0 Plsm concnrion (mulipl dos) 0 1 P (mulipl dos) 0 mx 1 Tim of mximum concnrion (mulipl dos) 1 ln 1 mx Avrg concnrion (sdy s) F L lrnc os F l AU l V d Equions/Usful_phrmcoinic_qu_5127 1

20 onsn r infusion Plsm concnrion (during infusion) 0 1 L Plsm concnrion (sdy s) 0 L lculd clrnc (hiou quion) 2 2 Vd L Shor-rm infusion P (singl dos) mx( 1) 1 LT T Trough (singl dos) T min( 1) mx( 1) P (mulipl dos) mx LT 1 1 T Trough (mulipl dos) lculd p 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 T [ mx 1 T T ( min )] lculd rcommndd dosing inrvl ln mx( dsird ) min( dsird ) T lculd rcommndd dos VT mx( dsird ) 1 1 T Two-omprmn-Body Modl T min mx lculd liminion r consn mx ln min wih * mx = msurd p nd * min = msurd rough, msurd ovr h im inrvl b Equions/Usful_phrmcoinic_qu_ AU / b / Vd Vd Vc r rinin lrnc L L cr cr ss ( 140 g) wigh ( ml) 72 p cr ( 140 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

21 K for minoglycosids K = (rL) Mbolic nd Rnl lrnc E H = lin fub Q l fu H in b l H = E Q = H H QH lin fub Q l fu H in b F H = Q H Q H l in fu b l rn = RBFE = GFR in in ou l rn = l rn = l rn = r of xcrion plsm concnrion R of scrion - R of rbsorpion fu GFR Plsm concnrion 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*(TBW-IBW) Volum of isribuion V V P V V P lrnc l os AU l V d V V T T K P fu fu T Equions/Usful_phrmcoinic_qu_5127 3

22 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 1 n( ) V 1 p: = 0; sdy s n rough: = mx ss 1 V ( 1 ) min ss mx ss If h dosing involvs h us of I.V. infusion: For singl shor-rm I.V. infusion: Sinc = for mx T 1 mx min VT mx ( T ) For mulipl shor-rm I.V. infusion sdy s: T 1 mx V T 1 min mx ( T ) Ls modifid 2010 :\urrn \ph5127_os_op_i\quions\ quions.doc

23 Ls modifid 2010 :\urrn \ph5127_os_op_i\quions\ quions.doc If h dosing involvs I.V. infusion (mor quions): T T V 1 (mos gnrl q.) during infusion = T so, T V 1 (during infusion) sdy s, -, 0 so, L V T V pss 0 0 (sdy s) rmmbring T 0 nd V L If h dosing involvs orl dminisrion: For singl orl dos: V F 1 ln mx For mulipl orl doss: V F ln mx