Drug Elimination and Multiple Dosing

Question 1

Repetitive Dosing

Answer 1

It take 4-6 half-lives to reach steady-state

Its usually 3.3t

Question 2

Loading Dose

Answer 2

Higher dose is given initially before dropping down to a lower maintenance dose
Depends on Vd
Loading Dose = TC*Vd/F

Does not reduce the time it takes to get to steady state, just gives you higher concentrations

Question 3

Maintenance Dose

Answer 3

Strategy to maintain a steady state of drug in the body
Based on replacing the amount of drug cleared from the body since the previous drug administration
Depends on CL
Maintenance Dose = CLTCT/F

Question 4

Steady State

Answer 4

Attained after approximately four half-lives

Time to steady-state independent of dosage

Question 5

Fluctuations

Answer 5

Proportional to dosage interval/half-life

Blunted by slow absorption

Question 6

Steady State Concentration

Answer 6

Proportional to dose/dosage interval

Inversely related to CL/F

Question 7

First-order Elimination

Answer 7

Elimination rate of the drug is a constant fraction of the drug remaining in the body (rather than a constant amount of drug per hour)

Half life stays the same

Question 8

Zero-order Elimination

Answer 8

When metabolic pathways are saturated, metabolism occurs at a fixed rate, i.e. it does not change in proportion to drug concentration

Half life changes

Question 9

Dose-dependent kinetics

Answer 9

When a drugs’s elimination is mediated by metabolism, its elimination will follow 1st order when concentration are below the Km of the metabolic enzymes, but follows 0-order at doses exceeding the Km of metabolic enzymes

Question 10

Elimination Clearance

Answer 10

Volume of PLASMA cleared of drug per unit time

Units are mL/min or L/hr

Question 11

Dose Adjustment in Renal Insufficiency

Answer 11

Reduced clearance of drugs that are eliminated primarily by the kidneys
Daily drug dose must be reduced by the ratio of measured clearance in renal failure over expected normal average clearance

Dosing rate normal x CLrf/CLn

Question 12

Determinants of Hepatic Drug Clearance

Answer 12

1. Hepatic blood flow (rate of drug deliver to eliminating organ)
2. Plasma protein binding (fraction of drug available for clearance)
3. Intrinsic Clearance (hepatocellular metabolism and/or biliary excretion)

Question 13

Restrictive Hepatic Clearance

Answer 13

Drugs with low hepatic extraction

A change in binding or drug metabolism/excretion will have a greater effect on hepatic clearance than changes in liver blood flow

Capacity-limited clerance

Question 14

Non-restrictive Hepatic Clearance

Answer 14

Drugs with high hepatic extraction

Sensitive to changes in liver blood flow, conditions that reduce hepatic blood flow (CHF, hypotension) will reduce hepatic clearance