Pharmacokinetics

Question 1

Oral Route Absorption

Answer 1

• crossing of drug from one water compartment, across epithelial membranes, into another water compartment

Question 2

Factors Involved in Absorption from Water Solution

2

Answer 2

• ** Lipid-To-Water Partition Coefficient - Drug Lipophilicity (Hydrophobicity)
• Ka of pKa of a Drug

Question 3

Lipid-To-Water Partition Coefficient - Drug Lipophilicity (Hydrophobicity)

Answer 3

• best predictor of drug entry into the body
• measured by using a two-phase mixture of water and a hydrophobic solvent and allowing drug to equilibrate between the two phases
• the higher the ratio, the more readily the drug will leave the water phase on the luminal side of the GI tract and enter the water phase on the plasma side of the GI epithelium

Question 4

Lipid/Water Partition Coefficient (P)

equation

Answer 4

[Drug] in Lipid Phase
________________
[Drug] in Water Phase

• great P = better= greater drug absorption*
• P = hydrophobicity parameter*

Question 5

ka/pKa of Drug

Answer 5

ONLY UNCHARGED DRUGS can move across biological membranes

• protonated weak acids
• deprotonated weak bases

Question 6

To predict the fraction of total drug molecules that are in the protonated and unprotonated states:

Answer 6

• need to know the drug pKa and the ambient pH
• ** use HH equation***
• pKa is a very important predictor of drug absorption when we know the pH of the site

Question 7

pH Partition Hypothesis

Answer 7

• ability of drug to be absorbed
• AT EQUILIBIRIUM, THE TOTAL DRUG CONCENTRATION (UNCHARGED + CHARGED FORMS) IS HIGH IN THE COMPARTMENT WITH THE HIGHER DEGREE OF pH-DEPENDENT IONIZATION*
• UNCHARGED form will move toward equilibrium
• whichever compartment the drug is most ionized/charged based on pH will be where the drug will accumulate the most*

Question 8

pH Partition Hypothesis Key Point

Answer 8

• whichever compartment the drug is most ionized/charged based on pH will be where the drug will accumulate the most*
• drug always stuck in compartment where it is ionized (charged can’t pass through membrane)

Question 9

HH Equations

Answer 9

make ratio so uncharged species = 1

Question 10

Oral Bioavailability

Answer 10

• defined as the fraction (often given as %) of administered drug that gains access to the systemic circulation of the body in a chemically unaltered form
• ** not all of drug you swallow is available to do work!***

Question 11

% Bioavailability equation skip

Answer 11

amount of drug required for efficacy (mg)
_______________________________ = amt dose need
% bioavailability

Question 12

Volume of Distribution (Vd)

Answer 12

• VOLUME CONSTANT that relates the amount of drug in the body (Ab) and the plasma concentration (Cpl) generated by that amount
• Ab - amount of drug in the body that is BIOAVAILABLE!*
• Cpl - target: safe and effective amount*
• Vd is typically normalized to body weight (L/Kg)

Question 13

Drug Elimination (two ways)

Answer 13

• drug metabolism

- renal elimination

Question 14

Drug Metabolism

Answer 14

• metabolism reduces lipid solubility, thereby increasing susceptibility to urinary excretion
• liver enzymatically alters drug for excretion

Question 15

Renal Elimination

Answer 15

• the passage of drugs through the kidney and, ultimately, into the urine
• eliminate directly and unaltered

Question 16

Clearance (CL)

Answer 16

• volume plasma from which, over a specified interval of time, all drug present is removed

Question 17

Total Body Clearance (CLbody)

Answer 17

• typically involves the kidney (renal clearance) and the liver (hepatic clearance), with clearance at these sites being additive
• Normalize for body weight!!*

CLbody = CLrenal + CLhepatic
(given)

Question 18

Clearance at an Organ

Answer 18

CLorgan = Organ Plasma Flow (OPF) + Extraction Ratio (ER)
(given)
ER - the fractional decline in drug concentration from the arterial to the venous side of the organ
— input, clearance, output = % decline
— input vs output = ER

Question 19

Half-Life (t1/2)

Answer 19

the time it takes for the plasma concentration or the amount of drug in the body to be reduced by one-half (50%)

Question 20

Half-life provides an indication of:

Answer 20

1. The time to attain steady state after a dosage regimen is initiated or changed
2. The time for a drug to be removed from the body
3. ** The appropriate dosing interval for a drug **

Question 21

Absorption’s effect on Cpl

Answer 21

absorption increases Cpl

IV drugs bypass absorption

Question 22

Distribution and Elimination’s effect on Cpl

Answer 22

both decrease Cpl

Question 23

2 Major Patterns by which Drugs are Administered

Answer 23

1. CONTINUOUS administration at a constant rate (IV)

2. DISCONTINUOUS administration in which the patient takes chronic repeated doses at specific intervals

Question 24

Steady State IV Infusion (Cpl-ss)

Answer 24

when drug in = drug out

• on chart IV infusion looks like enzyme vmax chart (except Vmax = Cpl-ss)
• ** depends soley on infusion rate Ro!***

Question 25

Rate of Infusion (Ro)

Answer 25

• the rate of entry into the body; constant with time

Question 26

Ro Steady state

Answer 26

Ro = CLbody x Cpl-ss
(given)
CLbody: constant

Question 27

4 half-lives role of thumb

Answer 27

4 half-lives must elapse for an approximation of the steady state condition (the “Vmax” (Cpl-ss) on the infusion chart)

Question 28

Half-lives vs % Steady State Chart

Answer 28

1: 50
2: 75
3: 87.5
* 4:94* aka close enough to steady state

Question 29

Chronic Dosage Regimen Considerations

Answer 29

DISCONTINUOUS

1. Half-life
2. Therapeutic Index

Question 30

Commonly Employed IV Regimen

Answer 30

• Start with 2x effective dose of the drug (LOADING DOSE; only different dose given)
• Repeat with effective dose every half-life of the drug (MAINTENANCE DOSE)

Only works for drugs in which

• the half-life is convenient (between 8-24 hrs)
• the 2-fold fluctuation in drug amount is acceptable

Question 31

For any good regiment, you never want to fall ____ ____

Answer 31

below efficacy

Question 32

Chronic Oral Dosage Regimens

Answer 32

• have same considerations that apply to IV, but ADJUSTED for BIOAVAILABILITY

Question 33

Most Common Pattern of Drug Administration!

Answer 33

Fixed Dose and Fixed Time Regimens

• doses overlap
• drug accumulates until its concentration increases to a steady state point where the rate of loss = rate of input