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

Transcription

1 UFI: PHA 527 Scond Exm Fll 2006 On my honor, I hv nihr givn nor rcivd unuhorizd id in doing his ssignmn. Nm Pu ll nswrs on h bubbl sh OAL /60 ps

2 UFI: Qusion S I (ru or Fls) (25 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 or fls for drug A, which is clrd only by hpic mbolism nd hs L o of 80 L/h : F his drug is low xrcion drug 2: F h clrnc of nohr drug limind only by h idny (only filrd no rbsorbd) will b smllr hn h of rug A 3: F h orl biovilbiliy of his drug will b significnly smllr hn 80% 4: F h orl biovilbiliy will dpnd on livr blood flow 5: F rug, nown o induc nzyms lso rsponsibl for mbolism of rug A will significnly ffc h clrnc of rug A 2

3 UFI: Qusion S II (5 poins) Imgin high xrcion drug h is only limind vi hpic mbolism. wo pins hv bn injcd wih h sm dos of his drug. hy show h following phrmcoinic propris mx [μg/ml] K [/h] Vd [L] L [L/h] F (%) 6 6: A lis of physiologicl prmr is shown blow. Idnify h on physiologicl prmr h would xplin ll diffrncs in bov phrmcoinic prmrs Prmr- A. GFR B. f u. f u. Q hp E l in 3

4 UFI: Qusion S III (Mching) (20 poins) For h physiologicl chngs lisd blow, slc h inducd chngs on h phrmcoinic prmrs for lipophilic, unionizbl (no cid or bsic group in h molcul), proin bound drug h is limind only hrough h idnys (som nswrs my b usd mor hn onc). Slc h ffc on inics (A) l REN (B) l HEP () V () orl biovilbiliy F (E) fcor no lisd in A- Physiologicl chng 7: crs in plsm proin binding 8: Incrs in issu binding 9: crs in livr blood flow 0: Incrs in urin flow 4

5 UFI: Qusion S IV (Mching) (20 poins) (Assum GFR is 30 ml min -, urin flow is.5 ml min - ) For h following siuions, indic whhr h drug is: Slc from h following choics: (A) filrd (B) rbsorbd () civly scrd () rbsorbd hrough rnsporrs : A drug wih f u 0.02nd l REN 20 ml min - is 2: A drug wih f u 0.40 nd l REN 52 ml min - is 3: A drug wih f u 0.60 nd l REN 0.9 ml min - is 4: A drug wih f u.0 nd l REN 0.3 ml min - is 5

6 UFI: Qusion S V (0 poins) A hydrophilic drug (prdominnly ionizd ph7.4) is limind only by h idny. Plsm proin binding is 90%. Glomrulr filrion r is norml (30 ml/min). Urin flow is 2ml/min. No civ rnl scrion or civ rbsorpion fr rnl filrion is obsrvd. h volum of disribuion is 40 L. 5: Wh is h clrnc? (0 poins) A. 0.5 ml/min B. 3 ml/min. ml/min. 30 ml/min 6: 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 55 %. A ml/min B. 30 ml/min. 65 ml/min ml/min E ml/min 6

7 UFI: Qusion S VI (20 poins) 7: 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. 93 ml/min. 03 ml/min E. non of h bov 7

8 UFI: Qusion S VII h sm dos of Alprzolm ws givn ihr lon or wih oconzol. Explin wh is going on by slcing h corrc nswr from h following lis. (5 poins) : h clrnc of lprzlm is incrsd in h prsnc of Koconzol. 2: Alprzlm is lily o b low xrcion drug. 3: Koconzol dcrss h volum of disribuion of Alprzolm, hrby incrsing h hlf-lif of h drug 4: Koconzol is lily o incrs livr blood flow. 8. h corrc nswr is: A. B. 2. 3, 4. 2, 3 E., 2, 3, 4 8

9 UFI: Qusion S VIII (ru or Fls) (30 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) 9: F h rnl clrnc of drug dpnds h issu binding of h drug. 20: F h hlf-lif of drug incrss wih incrsing issu binding. 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 h rnl clrnc of minoglycosids 23: F For n cidic drug wih p of 2.0, djusmn of h urin ph wihin physiologicl rngs will significnly chng h rnl clrnc. 24: F For drug wih linr phrmcoinics, hpic clrnc dpnds on h drug plsm concnrion, s h r of mbolism incrss wih incrsing drug concnrions in h blood. 9

10 UFI: Qusion S IX (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). Assum linr phrmcoinics for ll qusions. 25: F h lrgr h volum of disribuion, h smllr h AU of givn drug. 26: F oubling h dos will doubl h AU of drug 27: F An incrs in fu will dcrs AU of high-xrcion drug givn orlly. 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 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

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