PHA Exam 1. Spring 2013

Transcription

1 PHA 5128 Exam 1 Spring Antibiotics (5 points) 2 Body Wight/Pdiatrics (5 points) 3 Rnal Disas (10 points) 4 Aminoglycosids (5 points) 5 Amikacin (10 points) 6 Gntamicin (10 points) 7 Aminoglycosids (5 points) 8 Bioavailability (10 points) 9 Basic Principls (10 points) 10 Basic Principls (5 points) 11 Basic Principls (10 points) 12 Basic Principls (5 points) 13 Antibiotics (5 points) 14 Aminoglycosids (5 points)

2 Problm 1 (5 points) An antibiotic pharmacokintic bhavior is bst dscribd by a 2-compartmnt modl. Th drug is administrd as an intravnous bolus and its pharmacokintic profil is bst charactrizd by th following quation, C(t) = t t whr th concntration is in mg/l and tim is in hour. Estimat th ara undr th curv and dtrmin whthr th AUC/MIC ratio is gratr than 400 if th MIC against th infction is 2 mg/l. Us th following quation to comput th AUC AUC = A α + B β A. AUC = 432 mg*h/l; AUC/MIC ratio is gratr than 400 B. AUC = 834 mg*h/l; AUC/MIC ratio is gratr than 400 C. AUC = 417 mg*h/l; AUC/MIC ratio is lss than 400 D. AUC = 208 mg*h/l; AUC/MIC ratio is gratr than 400 E. AUC = 417 mg*h/l; AUC/MIC ratio is gratr than 400 AUC = A α + B β = = 417 mg h/l AUC MIC = = 208

3 Problm 2 (5 points) Which of th following statmnts about body wight ar TRUE? (1) Obs patints may xprinc an ovrdos of a wakly or modratly lipophilic drug compard to a patint with idal body wight if th total body wight basd dosing approach is usd, sinc thy ar poorly distributd in obs patints. (2) Th total body watr (in % of body wight) in nonats is usually smallr than that in adults. (3) Lipophilic drugs tnd to hav a largr volum of distribution whn givn to patints with an incrasd body wight compard to patints with an idal body wight (4) Th plasma protin binding of drugs in nonats is usually lss than in adults. A. 1&2&3 B. 2&4 C. 3&4 D. 1&3&4 E. All th statmnts ar corrct

4 Problm 3 (10 points) Aftr masuring hr srum cratinin concntration, you calculat th cratinin claranc of a 20 yar old fmal patint (60 kg, 165cm) to b 6 L/h. What is hr srum cratinin concntration? A mg/dl B mg/dl C µg/dl D µg/dl E. Th information providd is not nough to answr th qustion IBW=45+0.9(hight in cm-150)=45+0.9( )= =58.5 kg TBW % 102.6% 120% IBW 58.5 Sinc TBW is lss than 120% of IBW, w should us TBW as dosing wight to calculat cratinin claranc CLcr=6 L/h=100 ml/min Cp cr (140 ag) BW (140 20) mg dl CL cr

5 Problm 4 (5 points) J.C. is a 57 kg fmal patint with mthicillin-rsistant S. aurus infction. Which of th following would b a rcommndd dosing rgimn if th tobramycin plasma concntration was 8mg/L at 8 hours aftr th start of th infusion? Plas assum avrag population PK paramtrs for J.C. and us th nomogram that is givn blow. A. 400mg Q24h B. 500mg Q24h C. 400mg Q36h D. 500mg Q36h E. 400mg Q48h

6 Problm 5 (10 points) A 9-yar-old boy is hospitalizd with possibl bactrial infction. 500 mg amikacin (IV infusion for 45 min, Q12h) was givn for svral days. Th dosing tim is 8 am and 8 pm. His plasma sampls at stady stat wr analyzd and th rsults ar listd as follows: Tim Concntration 9 am 30 µg/ml 6:30 pm 4 µg/ml Calculat th volum of distribution (round appropriatlty). A. 12 L B. 16 L C. 20 L D. 24 L E. 30 L k C max ln 30 ln Cmin t 9.5 h 1 t1=0.25h, t2=1.5h C C g ml 1 max max kt C C g ml kt min min Dos Vd 15.9L k T C C kt (1 ) 500 (1 ) kt ( max min ) ( )

7 Problm 6 (10 points) A 40 yar old fmal patint, who suffrs from post-surgical wound infction, has bn tratd with gntamicin for svral days. Sh is 5 2 tall and 55 kg wight. Hr srum cratinin is 1.5 mg/dl. Th gntamycin is givn by IV infusion ovr 30 min with dos of 7mg/kg onc daily. Calculat th masurd pak concntration on hour aftr th infusion was startd? (Round appropriatly) A. Cmax=15 mg/l B. Cmax=20 mg/l, C. Cmax=25 mg/l D. Cmax=30 mg/l E. Cmax= 35 mg/l IBW=45+2.3(hight in inchs-60)=45+2.3(62-60)=45+4.6=49.6 kg TBW % 110.9% 120% IBW 49.6 Sinc TBW is smallr than 120% of IBW, TBW will b usd to calculat cratinin claranc (140 ag) BW (140 40) 55 CL CLcr 43.1ml min 2.6 L h Cp Vd 0.25 L kg 55kg 13.75L k cr CL h Vd τ=24h and T=0. 5h C 1 Dos mg L 1 1 Vd k T ( ) ( ) kt max k t1=0.5h, C C mg L kt max max

8 Problm 7 (5 points) Which of th following statmnts about aminoglycosids ar TRUE? 1. Th volum of distribution of aminoglycosids is usually 0.25 L. 2. Aminoglycosids ar mostly clard by th kidny. 3. Thraputic drug monitoring is not rcommndd for aminoglycosids. 4. Thr tims daily dosing is highly rcommndd for aminoglycosids. 5. A patint s cratinin claranc can b usd to stimat his total systmic claranc. A. 1&2&5 B. 1&3&4 C. 2&5 D. 1&5 E. All th statmnts ar corrct

9 Problm 8 (10 points) Basd on th tabl of pharmacokintic paramtrs obtaind aftr a 50 mg dos of drug A, plas calculat th bioavailability of drug A for th thr ag groups Ag group (yars) CL (L/h) T1/2 (h) Oral AUC (mg h/l) A. F20-39=0.35, F40-59 =0.47, F60-79=0.79 B. F20-39=0.30, F40-59 =0.34, F60-79=0.41 C. F20-39=0.25, F40-59 =0.29, F60-79=0.53 D. F20-39=1, F40-59 =0.84, F60-79=0.61 E. F20-39=0.44, F40-59 =0.59, F60-79=1 Dos F AUC CL F F F AUC CL Dos AUC CL Dos AUC CL Dos

10 Problm 9 (10 points) How will an incras in plasma protin binding affct th claranc (CL), bioavailability (F), and AUC, of a low-xtraction drug? (Plas not that mans no chang) (10 points) A. CL, F, AUC, B. CL, F, AUC C. CL, F, AUC D. CL, F, AUC E. CL, F, AUC Q CL f int u CL Q E Q CL int f u Q CLint f CL f CL u int u CL f Q F CL f Q CL f Q AUC int u 1 E 1 1 int u int u Dos int u Dos F Q Q CL f Dos CL Q CL f Q CL f CL f int u int u int u

11 Problm 10 (5 points) 10. Which statmnt is incorrct? A. Cratinin claranc is a masurmnt for kidny function. B. Bioavailability of high xtraction drugs is dpndnt on plasma protin binding. C. Claranc and volum of distribution dtrmin th half-lif of a drug. D. A multi-compartmnt-body modl has only on volum of distribution. E. Changs in claranc affct avrag stady-stat plasma lvls

12 Problm 11 (10 points) Drug B is administrd via multipl short-trm infusions. Dtrmin an appropriat dosing rgimn for a multipl two-hour infusion (dosing rat (R0) and dosing intrval) of drug B to achiv dsird stady stat plasma concntrations of 12.5 mg/l for th pak (drawn 2 h aftr th nd of a 2 h infusion) and approximatly 3.5 mg/l for th trough. Assum that drug B s plasmaconcntration-tim profil follows a on-compartmnt body modl. (CL = 15 L/h, VD = 100 L). Round appropriatly and us a clinically usd dosing intrval. A. R 0 = 815mg/h Q24h B. R 0 = 1630mg/h Q12h C. R 0 = 1630mg/h Q24h D. R 0 = 815mg/h Q12h E. R 0 = 815mg/h Q8h k = CL VD = 0.15 L h τ = ln(c pak,dsird) ln(c trough,dsird ) k + T + t = 1.27 h + 2h + 2h = h (round down to 12 h) 0.15 Dos = C pak,dsird CL T (1 k τ ) (1 k T )( k t ) 12.5 mg L 15 L h 2h (1 0.15h 1 12h ) = 1630 mg in 2 h or 815mg in 1h (1 0.15h 1 2h )( 0.15h 1 2h ) =

13 Problm 12 (5 points) Slct th incorrct statmnt A. In a on-compartmnt body modl, th volum of distribution dcrass with an incras in plasma protin binding B. In a two compartmnt body modl, th volum of distribution at stady stat (VDSS) is always largr than th volum of distribution of th cntral body compartmnt (Vc) C. Th plasma concntration at stady stat is a function of dosing rat (R0) and claranc (CL) D. In a two compartmnt body modl, VDara is not indpndnt of th claranc (CL) E. For a high xtraction drug, th fr plasma concntration at stady incrass with a dcras in tissu protin binding

14 Problm 13 (5 points) Which of th following statmnts is/ar tru rgarding cftazidim? (s graph blow). Th graph blow shows th fficacy paramtrs of cftazidim against K. pnumonia infction in nutropnic mic. Th targt lvl for fficacy is 7.2 log10 CFU/Thigh at 24 hours. i. Th ffct profil for this drug is a concntration-dpndnt on. ii. Th tim abov MIC is th paramtr of choic to valuat fficacy of cftazidim against K. pnumonia. iii. Th paramtr valu that achivs th minimum ffct is approximatly 35 hr abov MIC, which corrsponds to th targt valu of 7.2 log10 CFU/Thigh. iv. Th 24-hour AUC/MIC ratio gratr than 1000 is rquird to achiv th ffct of lowring th log10 CFU/Thigh blow 7.2. v. Incrasing th tim abov MIC, pak drug concntration and AUC/MIC ratio rsultd in a dcras in CFU, suggsting that this drug has bactricidal ffct. A. I, IV, V B. II, III, V C. II, III D. II, III, IV, V E. I, III, IV

15 Problm 14 (5 points) A 45-yar-old fmal patint (50 kg, 5 4, Cp,crat = 1.1 mg/dl,) is tratd with 100 mg gntamicin i.v. short-trm infusions (T = 30 min) Q8h. Assuming linar pharmacokintics (Vd=0.25L/kg, CL=ClCr), prdict th tru pak concntration at th nd of th infusion and th tru trough concntration bfor th nxt infusion at stady stat. A. Cmax: 8.79 mg/l Cmin : 1.41 mg/l B. Cmax: 6.79 mg/l Cmin : 0.85 mg/l C. Cmax: 8.79 mg/l Cmin : 1.85 mg/l D. Cmax: mg/l Cmin : 0.85 mg/l E. Cmax: mg/l Cmin : 1.41 mg/l IBW fmal = 45.5kg + 2.3kg (64 60) = 54.7kg TBW= 50 (kg) is smallr than IBW*120%, us TBW to calculat th Clcr C max,ss = CL Cr = (140 45) = 50.8 ml min = 3.05 L h k = CL L VD = 3.05 h L = kg 50kg h Dos (1 k T ) VD k T (1 k τ ) = 100mg ( h 0.5h ) 12.5L = h 0.5h ( h 8h ) mg L mg = L C min,ss = C max,ss k (τ T) = 8.79 mg L h 7.5h = 1.41 mg L