ĐÁP ÁN TỰ LUẬN TỔNG HỢP

IV BOLUS
 1. a. ke=(ln5.2-ln2.6)/(3-1)=0.3465 hr-1
  b. CLtot=Vd*ke=0.3465*50=17.325 L/hr

c. CLren=130 ml/min=7.8 L/hr

d. CLhep=17.325-7.8=9.525 L/hr

e. C=3.67e-0.3465*10=0.115 mg/L

 2. 
(1) ke =0.693 / t1/2 =1 hr -1 Vd =2∗80 =160 L Cl=ke •Vd
=1∗160=160 L/hr>90 L.hr There exists non-hepatic metabolism 
(2) AUC0-∞, = Dose/ Cl =45/160 = 0.28 mg. hr/ L

3.
Ke = ln C2 – ln C1/(t2-t1) = 0.20 /hr 

T1/2 = 0.693/ 0.2 = 3.45 hr 

C0 = Ct / exp( -ke * t) C0 = 1.13 mg/L

 Vd = dose / C0 Vd = 1200 / 1.13 = 1062 L 

CL = Vd * Ke = 1062 * 0.20 = 212.4 L/ hr 

AUC0-∞ = dose / Cl = 1200 / 212.4 = 5.65 mg.hr/L

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3.
a.Ans: Fasting condition – AUC (0-24hr) – 2.9688 mg*hr/L
Fed Condition - AUC (0-24hr) – 2.3364 mg*hr/L
b. Ans: Fasting Condition – Cmax: - 0.40 mg/ L at time 2.00 hr Fed Condition - Cmax: - 0.21
mg/L at time 4.00hr
c.Ans: The rate of absorption is faster in the fasting conditions compared to the fed conditions.
Using the Henderson-Hasselbach equation for weak acids we can see that weak acids are more
ionized at higher pH (pH >4) than when compared to lower pH values. This suggests that the
drug might have a higher solubility at intestinal pH compared to stomach pH. Therefore, in fed
conditions due to the delay in gastric emptying time, the rate of absorption is slower.
d) Ans: The extent of absorption is affected in fed conditions, which is reflected as a lower AUC
compared to the fasting conditions. One possible explanation could be that the drug might be
unstable in stomach conditions. Due to the delay in gastric emptying time the bioavailability is
reduced in fed state.