Lec 55: Pharmacokinetics I

Question 1

Zero order kinetics

Answer 1

constant rate of absorption or elimination

-LINEAR, M=kt

• speed is constant, rate of absorptionis independent of concentration gradient
• transport mechanism is saturated

Question 2

First order kinetics

Answer 2

• rate is proportional to the amount of drug still unabsorbed
• EXPONENTIAL, M= Mo(e)^(-kt)
• increase difference:increase speed
• [ ] is major determinant, gradient counts!
• not constant amount, constant fraction

Question 3

order Applications: Drug Absorption/Drug Elimination

Answer 3

zero order elimination - duration of a therapeutically effective drug [] increases linearly with amount in body fluids
first order elimination - duration of a therapeutically effective drug [] increases as the log of the amount in the body fluids does

Question 4

half life equation

Answer 4

half life = 0.693/ke

ke=rate constant of elimination

Question 5

Volume of Distribution

Answer 5

-apparent Volume in which the drug is distributed (a concept, not a real number)

Vd=(mg drug in body)/([]in plasma mg/L)

• as plasma [] decreases, Vd increases
• can be much higher than the total body volume if drug is nonhomogenously distributed with high [] in extravasculartissues (plasma [ ] is low in this case)

Question 6

Clearance

Answer 6

• expressed in L/hr or mL/min
• Volume of plasma cleared of drug
• CL is additive

CL=(rate of elimination in mg/hr)/([] drug in mg/L)

CL=(ke)(Vd)
half life=0.693Vd/CL

Question 7

Bioavailability

Answer 7

-fraction of unchanged drug reaching systemic circulation after oral administation (F)

F=f(1-ER)

ER= extraction ration in liver
f=fraction absorbed from gut

Question 8

Extent of absorption

Answer 8

ratio of drug entering blood circulation to total drug in digestive system
rate= extent *time

Question 9

First Pass Elimination

Answer 9

presystemic hepatic elimination; passes through liver before system circulation and may be metabolized or excreted into bile

-drug is decreased by : QCi - QCo, where Q= 90 L/h hepatic blood flow and Ci=drug entering liver, and Co = drug leaving

Hepatic CL= Q*ER

***if ER is large, we can compensate for low oral bioavailability by 1) increasing dose and 2) use alternative administative routes

Question 10

accumulation factor of a drug when the dosing interval is shorter than four half-live

Answer 10

accumulation factor = 1/(fraction lost in one dosing interval)

example: for a drug given once every half life, AF=2

Question 11

Dosing Regimen Construction

Answer 11

1. identify target [] that will produce desired effect - [] range between that causing ½ of greatest therapeutic effect (lower limit) and [] that will cause side effects in no more than 5-10% of all patients (uppe rlimit)
2. determine Vd and CL
3. maintenance dose
   a. dosing rate = CL*Css , where Css= []at steady state
4. if intermittent doses are given, then maintenance dose is determined by:maintenance dose=dosing rate* dosing interval
5. if target [] needs to be reached quick, and or elimination rate ke is small, loading doses might be applied: loading dose= Vd*Target []
6. check for desired effect and adjust

Question 12

Relate half lives to steady state

Answer 12

It takes 4-5 half lives to reach/change a steady state