PHRM 835 Exam 1 Random Info Flashcards
Which of the following is NOT a potential cause of low oral bioavailability (F)?
a. Extensive renal excretion
b. Incomplete intestinal absorption
c. Extensive hepatic metabolism
d. Significant first pass effect
a. Extensive renal excretion
F = Fa x Fg x Fh: significant first pass means significant hepatic metabolism after absorption (i.e., low Fh). This will lead to low F
What is F of an orally administered drug when it is completely absorbed and not metabolized in the liver or intestine (i.e., fraction metabolized ~ 0)?
a. 0
b. 0.1
c. 0.5
d. 1
d. 1
Fa = 1, Fg = 1, Fh = 1
F = Fa x Fg x Fh = 1
Which of the following statements on (absolute) bioavailability (F) is FALSE?
a. Changes in the extent of oral absorption are likely to lead to changes in F
b. F is the fraction of oral dose reaching systemic circulation
c. Drugs of low F will require a higher dose to obtain the same AUC, when compared to drugs of high F
d. Increased hepatic metabolism by enzyme inducers would lead to improved (i.e., increased) F
d. Increased hepatic metabolism by enzyme inducers would lead to improved (i.e., increased) F
(enzyme inducers would decrease F)
From literature, you find that AUCoral after administration of 100 mg Drug A is 100 μg·hr/L. What is oral clearance (CLoral) of Drug A?
a. 1000 L/hr
b. 100 L/hr
c. 10 L/hr
d. None of the above
a. 1000 L/hr
CLoral= oral dose/ oral AUC = 100000/100 (Ugxh/L) (look at units)
Which of the following CL would have the smallest values when pharmacokinetic property of a drug is as follows:
F: 0.5
Cb/Cp: 0.5
fe: 0.5
a. Systemic plasma clearance (CL)
b. Oral clearance (CLoral)
c. Blood clearance (CLb)
d. Renal clearance (CLr)
e. They all have the same value
d. Renal clearance (CLr)
CLr = fe * CL = 0.5CL
Which of the following statements on clearance is FALSE?
a. To estimate systemic CL, IV data (i.e., concentration-time profile after intravenous administration) is required
b. Depending on what matrix (e.g., plasma or blood) is used to measure drug concentration, different clearances can be estimated (e.g., systemic clearance or blood clearance)
c. The upper limit in CLoral values is cardiac plasma output.
d. CLpo can be estimated from oral data (i.e., concentration-time profile after oral administration)
c. The upper limit in CLoral values is cardiac plasma output.
(there is no upper limit in CLoral values)
Assume that blood-to-plasma concentration ratio is 0.5 unless indicated otherwise; Hepatic plasma flow is 0.7 L/min; Typical GFR = 120 and 1 ml/min. Drug B is eliminated entirely by hepatic metabolism. If CL of drug B is 300 ml/min, what is the hepatic extraction ratio (EH) of Drug B?
a. 0.86
b. 0.43
c. 0.22
d. None of the above
b. 0.43
Eh = CLh/Q = 300/700 = 0.43
Which one of those is NOT a characteristic of a high EH drug?
a. Significant first pass effect
b. Low bioavailability
c. Incomplete oral absorption
d. Good substrate of hepatic drug metabolizing enzymes
c. Incomplete oral absorption
Rifampin would change which of the following pharmacokinetic or physiological factors of interacting drugs when co-administered?
a. Intrinsic CL (CLint)
b. Hepatic plasma flow (QH)
c. Unbound fraction (fu)
d. All of the above
a. Intrinsic CL (CLint)
Assume that blood-to-plasma concentration ratio is 0.5 unless indicated otherwise; Hepatic plasma flow is 0.7 L/min; Typical GFR = 120 ml/min. Systemic (plasma) clearance of Drug C is 600 ml/min, and the drug is entirely eliminated by hepatic metabolism and completely absorbed from the intestine. Which one of the following findings is expected when cimetidine, an enzyme inhibitor, is co-administed?
a. Significantly increased AUCiv
b. Significantly increased CL
c. Significantly increased F
d. None of the above
c. Significantly increased F
Assume that blood-to-plasma concentration ratio is 0.5 unless indicated otherwise; Hepatic plasma flow is 0.7 L/min; Typical GFR = 120 ml/min. Systemic (plasma) clearance of Drug D is 100 ml/min, and 100% of this drug is found in the urine as its metabolites. When oral absorption of this drug is complete, which of the following statements is TRUE?
a. Bioavailability of this drug is expected to be high (i.e., F> 0.7)
b. The drug is a high hepatic extraction ratio drug.
c. Changes in hepatic plasma flow are likely to affect CL of this drug significantly
d. Changes in hepatic plasma flow are likely to affect F of this drug significantly
a. Bioavailability of this drug is expected to be high (i.e., F> 0.7)
(100% of drug were found in urine as metabolites, so mainly by hepatic metabolism, and fe = 0
Eh = CLh/Q = 100/700 = 0.14
So low Eh drug
CL = fu * CLint, F = 1 (when Fa = 1)
Assume that blood-to-plasma concentration ratio is 0.5 unless indicated otherwise; Hepatic plasma flow is 0.7 L/min; Typical GFR = 120 ml/min. Based on the information of Drug E given, which of the following statements is FALSE?
CL: 50 ml/min
fu: 0.95
fe : ~0
a. Hepatic metabolism is the major elimination pathway.
b. Hepatic enzyme inducers are likely to increase CL of Drug E significantly.
c. Urine pH adjustment is a plausible approach in cases of Drug E overdose.
d. Bioavailability of this drug is likely to be high when intestinal absorption is complete.
c. Urine pH adjustment is a plausible approach in cases of Drug E overdose.
(renal route is not a major drug elimination pathway here fe = 0. Urine pH adjustment likely won’t affect drug E elimination)
Assume that blood-to-plasma concentration ratio is 0.5 unless indicated otherwise; Hepatic plasma flow is 0.7 L/min; Typical GFR = 120 ml/min. Based on the information of Drug F given, which of the following statements is FALSE?
Property: Weak acid
CL: 300 ml/min
CLR: 300 ml/min
fu: 0.3
a. 100% of the parent drug is found in the urine.
b. A significant drug interaction with hepatic enzyme inducers is expected
c. A significant amount of drug is secreted in renal tubules
d. A significant drug interaction with probenecid is expected
b. A significant drug interaction with hepatic enzyme inducers is expected
(no hepatic metabolism is involved in drug G metabolism)
Assume that blood-to-plasma concentration ratio is 0.5 unless indicated otherwise; Hepatic plasma flow is 0.7 L/min; Typical GFR = 120 ml/min. Which of the following is expected to change significantly when rifampin is co-administered to Drug G, a high EH drug, when its intestinal absorption is complete?
a. AUCIV of Drug G
b. CL of Drug G
c. F of Drug G
d. None of the above
c. F of Drug G
(for high Eh drug, F = Qh/(fu * CLint)
Assume that blood-to-plasma concentration ratio is 0.5 unless indicated otherwise; Hepatic plasma flow is 0.7 L/min; Typical GFR = 120 ml/min. Warfarin is a low EH drug that is eliminated entirely by hepatic metabolism. Protein binding of warfarin is >99%. Which of the following is the expected finding when co-administered aspirin displaces warfarin from albumin?
a. Significantly increased AUCIV of warfarin
b. Significantly increased F of warfarin
c. Significantly increased CL of warfarin
d. None of the above
c. Significantly increased CL of warfarin
(low Eh drug, CL = CLh; CLh = fu * CLint. Inc in fu would lead to significant increase in CL)
Which of the following is a characteristic of low EH drugs when compared to high EH drugs?
a. Smaller CLH
b. Smaller F
c. Significant first pass effect
d. Significant renal excretion
a. Smaller CLH
β-blockers, such as propranolol, can decrease cardiac output and blood (or plasma) flow to the liver. Which of the following is the expected finding for a low EH drug when the drug is taken with propranolol?
a. Insignificant changes in AUCIV
b. Significant changes in F
c. Significant changes in AUCoral
d. Significant changes in CL
a. Insignificant changes in AUCIV
(low Eh drug -> CLh = fu * CLint. Not affected by changes in Q. AUCiv = dose/CL. If CL is not affected, AUCiv is not affected either)
Which of the following would promote (i.e., increase) renal excretion of a renally excreted drug?
a. Increased reabsorption
b. Increased secretion
c. Decreased filtration
d. All of the above
b. Increased secretion
Which of the following statement is TRUE when you want to manage overdose of renally excreted drugs?
a. Alkalinization of urine will increase secretion of metamphetamine
b. Alkalinization of urine can be used to promote renal excretion of metamphetamine
c. Acidification of urine will increase renal excretion of metamphetamine
d. Acidification of urine can be used to manage salicylic acid overdose
c. Acidification of urine will increase renal excretion of metamphetamine
hydrophobic compounds are perfusion/permeability limited
perfusion
hydrophilic compounds are perfusion/permeability limited
permeability
T/F: ionized compounds show poorer membrane permeability than un-ionized compounds
true
T/F: lipophilic compounds tend to show greater membrane permeability
true
T/F: lipophilic compounds tend to show permeability rate-limited distribution
false
T/F: decreased plasma protein binding of high protein-bound drugs will likely increase Vd
true
T/F: Vd is expected to be small for a drug that exhibits strong binding to tissue components
false
T/F: the time to reach the steady state depends on the dose
false
(Tss = 3.3 * T1/2)
T/F: doubling the dose will double the steady state concentration
true
(Css = Ro/CL)
T/F: doubling the dose will shorten the time to reach a steady state
false
what is flip-flop kinetics and what causes it?
a drug cannot be eliminated faster than it can be absorbed (absorption is driving rate of elimination when ka < kel); caused by slow absorption
which of these two, absolute bioavailability or relative bioavailability, is compared to IV?
absolute bioavailability
T/F: enzyme inducers of CYP3A4 would likely decrease the systemic exposure of CYP3A4 substrates
true
T/F: enzyme inhibitors of CYP3A4 would likely increase the systemic exposure of CYP3A4 substrates
true
