PHA Second Exam. Fall 2007

Transcription

1 PHA 527 Scond Exm Fll 2007 On my honor, I hv nihr givn nor rcivd unuhorizd id in doing his ssignmn. Nm Pu ll nswrs on h bubbl sh OAL /30 ps

2 Qusion S I (ru or Fls) (5 poins) ru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls Mr whhr h following smns s ru (A) or fls (B). rug A is clrd only by hpic mbolism nd hs n inrinsic clrnc of 80,000 L/h : F h orl biovilbiliy of his drug will b lrgr hn 80%. 2: F Plsm proin binding will ffc h orl biovilbiliy of his drug. 3: F h hpic clrnc of his drug is 333 L/min 4: F Plsm proin binding will ffc h hpic clrnc of his drug. 5: F rug B, nown o induc nzyms lso rsponsibl for mbolism of rug A, will significnly ffc h clrnc of rug A if givn oghr. 2

3 Qusion S II (8 poins) ru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls Imgin lipophilic unionizd drug A wih volum of disribuion of 08 L. Whn givn by n iv bolus injcion, h p concnrion of 0.8 μg is obsrvd ( o ). Whn givn orlly, h orl biovilbiliy is 99.9 %. Plsm Proin Binding is 50% (f u 0.5). P [ug/ml] 0.8 V [L] 08 F (%) 99.9 f u 0.5 Mr whhr h following smns r ru (A) or fls (B). 6: F h drug is highly mbolizd in h livr. 7: F Plsm proin binding will ffc h orl biovilbiliy of his drug. 8: F h hpic clrnc of his drug will b smllr hn h l rn 9: F Plsm proin binding will ffc h hpic clrnc of his drug 0: F rug B, nown o induc nzyms lso rsponsibl for mbolism of rug A will significnly ffc h clrnc of rug A : F rug B, nown o induc nzyms h r lso rsponsibl for mbolism of rug A is lily o dcrs h clrnc of A 3

4 Qusion S III (Mching) (20 poins) For h physiologicl chngs lisd blow, slc h inducd chngs on h phrmcoinic prmrs for hydrophilic srong cid, proin bound drug h is only limind hrough h idnys (som nswrs my b usd mor hn onc). Slc h ffc on inics (A) Orl Biovilbiliy F (B) l rn () V () orl biovilbiliy F (E) nohing hppns or ffc is no lisd Physiologicl chng 2: crs in plsm proin binding 3: crs in issu binding 4: crs in GFR 5: Incrs in urin flow 4

5 Qusion S IV (20 poins) A lipophilic cidic drug (p of 7) is limind only by h idny. Plsm proin binding is 90%. Glomrulr filrion r is norml (30 ml/min). Urin flow is 2ml/min.Urin ph is similr o h of blood (bou 7). h volum of disribuion is 40L. 6: Wh vlu dscribs bs h clrnc? (0 poins) A: 0.5 ml/min B: 3 ml/min : 30 ml/min : 6.6 ml/min E: non of h bov 7: Assum on comprmn body modl? Wh is h rnl clrnc of ypicl minoglycosid in pin showing crinin clrnc of 65 ml /min (0 poins). h plsm proin binding for his minoglycosid is 90 %. A: 58.5 ml/min B: 30 ml/min : 65 ml/min : 6.5 ml/min E: 35.8 ml/min 5

6 Qusion S V (0 poins) 8: Robr is vry sic nd nds rmn wih n minoglycosid. In ordr o sr him on h minoglycosid n iv bolus loding dos shll b givn. Your rsponsibiliy is o giv him h firs dos. In ordr o do so, you hv o sim Robr s crinin clrnc. Robr is 5 f 0 inchs ll, 34 yrs old, ml, nd wighs 280 pounds. His srum crinin is.5 mg/dl. Wh crinin clrnc do you com up wih? A: 72 ml/min B: 84 ml/min : 70 ml/min : 03 ml/min E: non of h bov 6

7 Qusion S VI (5 poins) 9: h following pins diffr in h (A) (B) () dos rcivd clrnc volum of disribuion P (mg/l) K (/h) /2 (h) AU (mg/l*h)

8 Qusion S VII (ru or Fls) (5 poins) ru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls Mr whhr h following smns r ru (A) or Fls (B) 20: F h rnl clrnc of drug (s drmind by filrion nd rbsorbion) lwys dpnds on h issu binding of h drug. 2: F o drmin h clrnc of drug, on nds o now whhr h drug is on or wo comprmn drug. 22: F rining lo of wr (urin flow is doubld) will incrs significnly h rnl clrnc of minoglycocsids 23: F For n cidic drug wih p of.0, djusmn of h urin ph wihin physiologicl rngs will significnly chng h rnl clrnc. 24: F Hpic clrnc dpnds on h drug plsm concnrion, s h r of mbolism incrss wih incrsing drug concnrions in h blood. 8

9 Qusion S VIII (ru or Fls) (2 poins) ru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls Mr whhr h following smns r ru (A) or fls (B) for drug h is minly limind hrough hpic mbolism. 25: F h lrgr h volum of disribuion, h smllr h AU of givn drug.. 26: F oubling h dos will gnrlly doubl h AU of drug fr iv bolus injcion 27: F An incrs in plsm proin binding will lwys rsul in dcrs of h drug s hpic clrnc 28: F An incrs in plsm proin binding will undr no circumsncs rsul in dcrs of h drug s hpic clrnc 9

10 Qusion S IX (5 poins) 29. Which of h following smns r corrc? ) W cn roughly ssum h chng in clrnc will rsul in chng in volum of disribuion. 2) rug A is 40% proin bound, drug B 98% proin bound. A wo prcn dcrs in plsm proin binding will b mos significn for drug A. 3) Gnic vribiliy in mbolizing nzyms lwys lrs hpic clrnc. 4) In gnrl, w should lwys us IBW for drug rcommndions for clculing crinin clrnc (L cr ) A) 2, 3, 4 B), 3 & 4 ) 2, 3 ) 3, 4 E) Non of h bov 0

11 Qusion S X (0 poins) 30. An invsigionl nw drug is limind nirly by livr (hpic) mbolism, wih clrnc of.35l/min in subjcs wih n vrg livr blood flow of.50l/min. Wh would b is xpcd clrnc in congsiv hr filur pin wih livr blood flow of.0l/min bu no chng in hpic xrcion rio? A).0L/min B).50L/min ).8L/min ) 0.99L/min E) nno b drmind bcus h dos is no givn.

12 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

13 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 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 wih * mx msurd p nd * min msurd rough, msurd ovr h im inrvl α + b 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 Wih wigh in g, g in yrs, crinin plsm conc. in mg/dl nd L cr in ml/min

14 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

15 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 F:\NEWRIVE\Ph528_os_Op_II\ quions\ quions.doc

16 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 F:\NEWRIVE\Ph528_os_Op_II\quions\ quions.doc