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

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1 Nm: UFI#: PHA 527 Finl Exm Fll 2008 On my honor, I hv nihr givn nor rcivd unuhorizd id in doing his ssignmn. Nm Pls rnsfr h nswrs ono h bubbl sh. Pls fill in ll h informion ncssry o idnify yourslf. h procors will lso collc your xms. ol poins : /85 poins Good LUK.

2 Nm: UFI#: Scion Qusion : For h quions dscribing consn r infusions. ( _5 ps) : h drug inpu is ssumd o b firs ordr procss 2: h drug inpu is ssumd o b zro ordr procss 3: h liminion is ssumd o b zro ordr procss 4: h liminion is ssumd o b firs ordr procss 5: h drug disribuion is modld s firs ordr procss 6: h drug disribuion is modld o b zro ordr procss. h corrc smn(s) for qusion r (is): A:, 3 nd 5 B: 2, 3 nd 6 : nd 3 : 2 nd 4 E: 4 nd 6 Qusion 2: W hv dfind svrl volums of disribuion whn ling bou 2 comprmn modl (5 poins). h volum of disribuion in 2 comprmn modl: : rls h moun of drug in h body o h plsm concnrion. 2: is dcrsing wih im fr drug dminisrion. 3: dpnds on clrnc during h b phs. 4: is no consn bcus i s im for h drug o nr nd lv h priphrl comprmn. 5: is no consn bcus fu chngs. 2. Slc h corrc smn(s) A: (, 2, 3, 4, 5) B: (, 3, 4, 5) : (, 2, 5) : (, 4, 5) E: (non of h bov) 2

3 Nm: UFI#: Scion 2: A 60 g pin is bgun on coninuous inrvnous infusion of rug X 36 mg/hr. Foryigh hours fr bgining of h infusion, h plsm concnrion is 2 mg/l. h liminion r consn is 0.55 h. 3. How mny hours will i o rch sdy s (5 poins) A: 8 h B: No nough informion o provid nswr. : dys : 2 3 dys E: 6 dys Qusion: If w ssum h his concnrion is sdy s, wh is h clrnc? (5 poins) 4 Mr A, B,, or, if h numbr in h ons column is (A), 2(B), 3(), 4(), 5(E). Lv bln if his is no h cs his would b E for 50 h) 5: Mr A, B,,, E if h numbr in h ons column is 6 (A), 7(B), 8(), 9(), 0(E) Lv bln if his is no h cs. You would lv his bln for 50 h) 6: Mr A, B,, or, if h numbr in h firs dciml column is (A), 2(B), 3(), 4(), 5(E). Lv bln if his is no h cs. You would lv his bln for 50 h) 7: Mr A, B,, or, if h numbr in h firs dciml column is 6 (A), 7(B), 8(), 9(), 0 (E) Lv bln if his is no h cs. his would b E for 50 h) 3

4 Nm: UFI#: Scion 3 : A 60 g pin is bgun on coninuous inrvnous infusion of rug X 36 mg/hr. Foryigh hours fr bginning of h infusion, h plsm concnrion is 2 mg/l. h liminion r consn is 0.55 h. Assum on comprmn modl. Qusion: Wh is h volum of disribuion in Lirs (0 poins) 8 Mr A, B,, or, if h numbr in h ns column is (A), 2(B), 3(), 4(), 5(E). Lv bln if his is no h cs his would b E for 50 l 9: Mr A, B,,, E if h numbr in h ns column is 6 (A), 7(B), 8(), 9(), 0(E) Lv bln if his is no h cs. You would lv his bln for 50 l 0: Mr A, B,, or, if h numbr in h ons column is (A), 2(B), 3(), 4(), 5(E). Lv bln if his is no h cs. You would lv his bln for 50 l : Mr A, B,, or, if h numbr in h ons column is 6 (A), 7(B), 8(), 9(), 0 (E) Lv bln if his is no h cs. his would b E for 50 l Scion 3 coninud: A 60 g pin is bgun on coninuous inrvnous infusion of rug X 36 mg/hr. Foryigh hours fr bginning of h infusion, h plsm concnrion is 2 mg/l. h liminion r consn is 0.55 h. h liminion r consn is 0.55 h. Assum on comprmn modl. If h infusion is coninud for 4 dys nd hn disconinud, wh would h plsm concnrion b 6 hours fr sopping h infusion? Pls prform clculions, w migh chc. (5 poins) 2 Mr A, B,, or, if h numbr in h ns column is (A), 2(B), 3(), 4(), 5(E). Lv bln if his is no h cs his would b E for 50 mg/ l 3: Mr A, B,,, E if h numbr in h ns column is 6 (A), 7(B), 8(), 9(), 0(E) Lv bln if his is no h cs. You would lv his bln for 50 mg/ l 4: Mr A, B,, or, if h numbr in h ons column is (A), 2(B), 3(), 4(), 5(E). Lv bln if his is no h cs. You would lv his bln for 50 m/ll 5: Mr A, B,, or, if h numbr in h ons column is 6 (A), 7(B), 8(), 9(), 0 (E) Lv bln if his is no h cs. his would b E for 50 m/l 4

5 Nm: UFI#: Qusion S 3 coninud: A 60 g pin is bgun on coninuous inrvnous infusion of rug X 36 mg/hr. Foryigh hours fr bginning of h infusion, h plsm concnrion is 2 mg/l. h liminion r consn is 0.55 h. Qusion: Wh infusion r would lily rsul in sdy s concnrion of 24 mg/l. (0 poins) Round pproprily. 6: Mr A, B,, or, if h numbr in h ns column is (A), 2(B), 3(), 4(), 5(E). Lv bln if his is no h cs his would b E for 50 mg/h 7: Mr A, B,,, E if h numbr in h ns column is 6 (A), 7(B), 8(), 9(), 0(E) Lv bln if his is no h cs. You would lv his bln for 50 mg/h 8: Mr A, B,, or, if h numbr in h ons column is (A), 2(B), 3(), 4(), 5(E). Lv bln if his is no h cs. You would lv his bln for 50 mg/h 9: Mr A, B,, or, if h numbr in h ons column is 6 (A), 7(B), 8(), 9(), 0 (E) Lv bln if his is no h cs. his would b E for 50 mg/h Scion 4: A 60 g pin is srd on 80 mg of gnmycin givn vry 6 hr s hr infusion. his pin is ssumd o hv n vrg volum of disribuion (vlu of h populion mn) of 0.25 L/g nd hlf lif of 3 hr. Qusion : Wh would b h plsm concnrion fr h firs infusion (on hour fr h sop of h infusion). Pls provid clculions (5 poins). Round pproprily. 20: Mr A, B,, or, if h numbr in h ons column is (A), 2(B), 3(), 4(), 5(E). Lv bln if his is no h cs his would b E for 5.0 mg/l 2: Mr A, B,,, E if h numbr in h ons column is 6 (A), 7(B), 8(), 9(), 0(E) Lv bln if his is no h cs. You would lv his bln for 5.0 mg/l 22: Mr A, B,, or, if h numbr in h firs dciml column is (A), 2(B), 3(), 4(), 5(E). Lv bln if his is no h cs. You would lv his bln for 5.0 mg/l 23: Mr A, B,, or, if h numbr in h firs dciml column is 6 (A), 7(B), 8(), 9(), 0 (E) Lv bln if his is no h cs. his would b E for 5.0 mg/l 5

6 Nm: UFI#: Scion 4 coninud : A 60 g pin rcivs 80 mg of gnmycin givn vry 6 hr s hr infusion. his pin is ssumd o hv n vrg volum of disribuion (vlu of h populion mn) of 0.25 L/g nd hlf lif of 3 hr. Qusion: Bsd on bov informion, wh is h flucuion sdy s h you cn xpc? Pls provid clculions. Round pproprily (5 poins) 24: Mr A, B,, or, if h numbr in h ons column is (A), 2(B), 3(), 4(), 5(E). Lv bln if his is no h cs. his would b E for 5 25: Mr A, B,,, E if h numbr in h ons column is 6 (A), 7(B), 8(), 9(), 0(E) Lv bln if his is no h cs. You would lv his bln for 5.0 mg/l 6

7 Nm: UFI#: Scion 4 (5 poins ch) h following qusions r rld o prs (blocs) of quions h r shown in h quion blocs A, B,,, E A: ( ) B: o L o ( L : ) : τ E: ' 26. Wh form of dminisrion is cpurd whn blocs A, B, nd E r muliplid oghr ( is no includd for his qusion)? Mr nswr in 26: (5 poins) A: singl iv bolus injcion B: mulipl orl bsorpion : mulipl bolus injcions : mulipl shor rm infusions E: singl consn r infusion Qusion : Idnify h bloc h bs dscribs o following. (20 poins) 27: A fcor suibl o qunify how much singl shor rm infusion is wy from h sdy s lvl h would b obsrvd if pin rcivs on infusion for long im. 28: his bloc cn b usd o clcul h rough concnrion sdy s from mx vlus, whn givn ihr s mulipl shor rm infusions or mulipl iv bolus injcions. 29: his bloc provids h mx fr drug is givn s s ingl shor rm infusion 30: his bloc provids h ccumulion ( sdy s) whn dos is givn dfind dosing inrvls 7

8 Nm: UFI#: Scion 5: Wh of h following smns r ru (A) or fls (B) (25 poins) 3: F If h rminl slop fr orl dminisrion is lss sp hn fr iv injcion, drug pricls migh dissolv vry slowly. 32: F If h firs pss ffc is surbl for givn drug, h fsr orl bsorpion, h highr will b h orl biovilbiliy 33: F For bioquivlnc, h r of h concnrion im profils is no imporn s bioquivlnc is only inrsd in h quivlnc of biologicl ffcs 34: F A wo comprmn body modl is usful o dscrib h plsm concnrions im profils of drugs h nr prs of h body slowly. 35: F h smllr L nd h lrgr h volum of disribuion, h lrgr h ccumulion of mulipl shor rm infusions. 8

9 Nm: UFI#: Scion 6: Pin nd 2 rcivd drug s n iv bolus injcion. Phrmcoinic nd physiologicl chrcrisics, such s dos, frcion of h drug unbound in plsm nd issu, inrinsic clrnc, livr blood flow, nd volum of plsm nd volum of h issu wr in hs pin r shown blow. Assum drug is clrd hrough livr mbolism. ABLE : INPU PARAMEERS Pin Pin 2 [mg] fu fu Li [L/h] Q [L/h] Vp [L] 3 3 VW [L] h nx bl shows h rsuling phrmcoinic prmrs in Pin. Pls circl in h fr column of h bl 2 for ch prmr whhr h prmr (P concnrion, K, V d, l, /2, E, F, AU) will b will b lrgr (A), bou h sm (B), or will b smllr () hn hos sims obsrvd in Pin. Mr on h bubbl sh h ppropri A, B, (40 poins) bl 2: OUPU PARAMEERS Qusion: Pin Pin 2 36 (5 poins) P[μg/ml].0 Lrgr (A), bou h sm (B), Smllr () 37 (5 poins) K [/h] 2.0 Lrgr (A), bou h sm (B), Smllr () 38 (5 poins) V d [L] 4 Lrgr (A), bou h sm (B), Smllr () 39 (5 poins) L [L/h] 8.8 Lrgr (A), bou h sm (B), Smllr () 40 (5 poins) /2 [h] 0.35 Lrgr (A), bou h sm (B), Smllr () 4 (5 poins) E 0.9 Lrgr (A), bou h sm (B), Smllr () 42 (5 poins) F [%] for bl 9. Lrgr (A), bou h sm (B), Smllr () 43 (5 poins) AU [μg/ml*h] 0.5 Lrgr (A), bou h sm (B), Smllr () 9

10 Nm: UFI#: Scion 7: (40 poins) 44. Which of h following fcors migh significnly ffc h rnl clrnc of n cidic drug (p 7) h hs molculr wigh of 200 lon? Assum urin ph of 7 (5 ps).. plsm proin binding 2. volum of disribuion. 3. Orl biovilbiliy 4. ph of urin 5. livr blood flow A:, 2, 3 B:, 4 :, 2, 4 :, 3, 5 E: non of h bov combinions Mr whhr h following smns r ru (A) or fls (B). (35 poins) 45 F Loding doss r minly givn for drugs wih smll volum of disribuion nd/or high clrnc 46 F Assum h h orl biovilbiliy of drug is 50%. If h orl bsorpion of his drug is vry fs, mx fr orl bsorpion will b bou hlf of h fr iv dminisrion. 47 F Assum h h orl biovilbiliy of drug is 50%. If h orl bsorpion of his drug is slow, mx fr orl bsorpion will b bou hlf of h fr iv dminisrion 48 F Afr iv bolus injcions, 200 mg givn vry 2 hours will rsul in h sm vrg pss hn 400 mg givn onc dy. 49 F 200 mg givn vry 2 hours will rsul in h sm AU hn 400 mg givn onc dy. 50 F rug A shows sdy s n ccumulion fr mulipl shor rm infusions of 4, rug B shows on of 2. rug B will chiv sdy s fs. 5 F Assum h hlf lif of drug o b 8hours. h drug should b givn vry 8 hours o chiv flucuion of 2. 0

11 Symbols Usful Phrmcoinic Equions dos τ 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 Vd 2 ln ln Hlf-lif Vd ln( 2) / L Inrvnous bolus rough (mulipl dos) τ 0 min τ Avrg concnrion (sdy s) pss Lτ Orl dminisrion Plsm concnrion (singl dos) F Vd im of mximum concnrion (singl dos) ln mx Plsm concnrion (mulipl dos) F Vd τ τ Iniil concnrion 0 Vd Plsm concnrion (singl dos) 0 Plsm concnrion (mulipl dos) 0 τ P (mulipl dos) 0 mx τ im of mximum concnrion (mulipl dos) τ ) ln τ ( ) mx Avrg concnrion (sdy s) F Lτ lrnc os F l AU l V d 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) 2 2 Vd ( 0 2) L ( 2 2 Shor-rm infusion P (singl dos) mx L ( ) rough (singl dos) τ min mx P (mulipl dos) mx L ( ) τ ( ) rough (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 [ mx ( ) ( min )] lculd rcommndd dosing inrvl ln τ mx( dsird ) min( dsird ) + lculd rcommndd dos V mx( dsird ) τ ( ) ( ) wo-omprmn-body Modl ( τ ) min mx lculd liminion r consn mx ln min Δ wih * mx msurd p nd * min msurd rough, msurd ovr h im inrvl Δ α + b Wih wigh in g, g in yrs, crinin plsm conc. in mg/dl nd L cr in ml/min Equions/Usful_phrmcoinic_qu_527 2 β AU / α + b / β Vd > Vd > Vc r rinin lrnc L L cr cr ss ( 40 g) wigh ( ml) 72 p cr ( 40 g) wigh ( fml) 85 p cr

13 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 l H + 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*(BW-IBW) Volum of isribuion V V P V V P lrnc l os AU l V d + V + V K P fu fu Equions/Usful_phrmcoinic_qu_527 3

14 For On omprmn Body Modl If h dosing involvs h us of I.V. bolus dminisrio n: For singl I.V. bolus dminisrion: 0 V 0 For mulipl I.V. bolus dminisrion: n( ) V ( n ) τ ( ) τ p: 0; sdy s n rough: τ mx ss V ( ττ ) min ss mx ss τ If h dosing involvs h us of I.V. infusion: For singl shor-rm I.V. infusion: Sinc τ for mx mx min V mx ( ) ( τ ) For mulipl shor-rm I.V. infusion sdy s: mx V min mx ( ) ( τ ) ( τ ) Ls modifid 2006 :\urrn \ph527_os_op_i\quions\ quions.doc

15 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 dminisrio n: For singl orl dos: V F ln mx For mulipl orl doss: τ τ V F ln mx τ τ Ls modifid 2006 :\urrn \ph527_os_op_i\quions\ quions.doc