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

Transcription

1 Nm: UFI#: PHA 5127 Firs Exm Fll 2014 On my honor, I hv nihr givn nor rcivd unuhorizd id in doing his ssignmn. Nm Qusion S/Poins I. 30 ps II. 20 ps III. 15 ps IV 15 ps V. 25 ps VI. 10 ps VII. 10 ps VIII. 10 ps IX. 35 ps TOTAL: 170 ps 1

2 Nm: UFI#: Qusion S I (Tru or Fls) (30 poins) Tru (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. 1: T F Th 1/2 of drug limind hrough zro ordr procss is drug spcific consn. 2: T F A lipophilic drug of low molculr wigh, cnno hv volum of disribuion h is smllr hn VT. 3: T F Th frcion of h drug bing limind pr hour is incrsing in firs ordr procss. 4: T F Two drugs h hv similr liminion hlf-livs will hv similr volums of disribuions. 5: T F Th sm dos of drug is givn orlly ihr s soluion or in form of slow dissolving crysl suspnsion. Th soluion will show highr mximum concnrions in plsm. 6: T F Whn hprin is ddd o blood nd h blood is cnrifugd, h rsuling suprnn is clld srum. 2

3 Nm: UFI#: Qusion S II (20 poins) Tru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls. Tru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls. onsidr lipophilic cidic drug A (p=14, logp=5, If you hv difficulis wih pk vlus: Th pk of Hl is clos o zro) nd lipophilic nurl drug B (logp=5). Boh do no show ny ffiniy o rnsporrs nd show similr issu nd plsm proin binding. 7: T F rug B will nr h brin fsr. 8: T F rug A will b unbl o nr h inrsiil fluid. 9: T F rug B b is lily o hv lrgr volum of disribuion 10: T F Th K of boh drugs will only diffr, if L diffrs. 3

4 Nm: UFI#: Qusion S III (15 poins) Lisd in h Tbl r wo propris of cidic drug molculs: h frcion unionizd ph=7.4 nd h priion cofficin of h unionizd form. RUG Frcion Unionizd Priion officin Molculr ph=7.4 of Unionizd form Wigh (lon) : Slc h corrc rn ordr wih which drugs 1-4 will nr brin issu. Assum h h drugs r no subjc o rnsporrs h blood-brin brrir. A) 1 slowr hn 2 slowr hn 3 slowr hn 4 B) 4 slowr hn 2 slowr hn 3 slowr hn 1 ) 4 slowr hn 2 slowr hn 1 slowr hn 3 ) 3 slowr hn 1 slowr hn 4 slowr hn 2 E) 1 slowr hn 3 slowr hn 2 slowr hn 4 4

5 Nm: UFI#: Qusion S IV (Tru or Fls) (15 poins) Tru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls. Assum no civ rnspor. 12: T F Assum drug is subsr of spcific rnspor proin. Trnsporrs only limin drugs from h body 13: T F Th r wih which hydrophilic compounds will mov cross wll-buil mmbrns will dpnd on h concnrion grdin bwn ol drug in plsm nd ol drug in issu. 14: T F Assuming h proin drug dos no bind o plsm nd issu componn, h volum of disribuion is lily o b 41 lirs. 5

6 Nm: UFI#: Qusion S V (Tru or Fls) (25 poins) onc. (ng/ml) Tim (h) onc. (ng/ml) Tim (h) rug A rug B Tru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls 15: T F rug B s r of liminion is ffcd by h moun of drug in h body. 16: T F rug A s liminion r consn hs h uni ng/ml. 17: T F For drug B, h frcion of drug limind pr hour is consn. 18: T F rug A s concnrion-im profil migh b xplind by surd mbolic nzyms. 19: T F For drug A, h liminion r consn dos no dpnd on h moun of drug in h body. 6

7 Nm: UFI#: Qusion S VI (10 poins) 20: An invsigionl nw drug is limind nirly by hpic mbolism, wih clrnc of 1 L/h in hlhy subjcs. Assum n vrg livr blood flow of 80 L/h in hs hlhy subjcs. Wh would b h xpcd clrnc in congsiv hr filur pin wih livr blood flow of 66 L/h? Us h mos ppropri rlionships A) 0.83 L/h B) 1.0 L/h ) 0.66 L/h ) 66 L/h E) Non of h bov 7

8 Nm: UFI#: Qusion S VI 21: A drug hs n inrinsic clrnc of 40,000 L/min. Th plsm proin binding nd livr blood flow r 60% nd 80 L/h, rspcivly. lcul h hpic clrnc. A) 80 L/h B) 35 L/h ) 48 L/h ) 320 L/h E) Non of h bov 8

9 Nm: UFI#: Qusion S VII (10 poins) 22: Assum drug A is prdominnly clrd hrough hpic mbolism. rug A hs n inrinsic clrnc of 40,000 L/min. Th plsm proin binding nd livr blood flow r 60% nd 80 L/h, rspcivly. How will h incrs in boh issu binding nd livr blood flow ffc h iniil concnrion (0 whn givn s i.v. bolus), hpic clrnc (L), biovilbiliy (F) for bl, AU, nd hlf-lif (1/2)? (Pls no h mns: bou h sm) A) 0, L, F, AU, 1/2 B) 0, L, F, AU, 1/2 ) 0, L, F, AU, 1/2 ) 0, L, F, AU, 1/2 E) 0, L, F, AU, 1/2 9

10 Nm: UFI#: Qusion S VIII (10 poins) 23. A nw nlysis chniqu hs nbld you o msur h drug concnrion bfor nd fr h blood psss h livr. Th plsm concnrions bfor nd fr h livr ws pssd wr 6.5 nd 2.4 mg/ml, rspcivly. lcul h hpic clrnc (ssum livr blood flow of 1450 ml/min). A) 15 L/h B) 35 L/h ) 55 L/h ) 75 L/h E) Non of bov 10

11 Nm: UFI#: Qusion S IX (35 poins) Mr A for Tru or B for Fls 24: T F Fr drug concnrions r lwys h sm in plsm nd issus, whn h disribuion occurs insnnously. 25: T F Enzym inducion ffcs h hpic clrnc of low nd high xrcion drugs 26: T F Enzym inducion ffcs h orl biovilbiliy of high xrcion drugs 27: T F A fs bsorpion migh llow lss frqun dosing. 28: T F A slowr bsorpion migh b dvngous for drug wih nrrow hrpuic window. 29: T F Th Fic s lw is: dq/d=*k*(plsm-issu)/h. Th concnrion rms (plsm nd issu )rfr o ol drug concnrions in ihr plsm or issu. 30: T F oncnrions in plsm r of rlvnc for drug hrpy s hy gnrlly corrl wll wih concnrions obsrvd h ffc (rg) si. 11

12 Nm: UFI#: 12

13 Nm: UFI#: 13

14 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

15 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

16 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

17 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

18 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