Flashcards in Drug Elimination & Multiple Dosing Deck (18):
Define loading dose. How is calculated?
large dose given initially to reach therapeutic levels quickly (followed by lower maintenance dose or infusion to sustain target concentration levels)
LD = TC x Vd/F
(depends on Vd)
Define steady-state concept.
steady-state is the maintenance of the target concentration (therapeutic range). Loading doses help reach target concentration faster, BUT it will still take 4-6 half-lives to reach steady state independent of dose)
List the primary pharmacokinetic parameters. How are they used to determine loading dose and maintenance dose?
- clearance determines MD
- Vd determines LD
Define maintenance dose.
- based on amount of drug cleared from the body since last administration
- maintains steady state after target has been reached
MD = CLxTCxT/F
(depends on CL)
Describe the concept of repetitive dosing.
Typically, it takes 4-6 half-lives to reach steady state (maintaining target concentration). With continuous infusion, it takes a long time to reach target concentration and then it plateaus off. By giving repetitive doses, you reach target concentration faster.
Compare/Contrast elimination and intercompartmental clearance.
EC: irreversible drug removal from the plasma through an eliminating organ; unidirectional
IC: drug distribution between plasma and tissues (bidirectional)
Define first order elimination.
- constant fraction of the drug is being eliminated from the body
- constant half life
- ex: lidocaine
Define zero-order elimination.
- drugs eliminated primarily by metabolism
- constant amount of the drug is being eliminated from the body
- elimination does not change with dosage b/c metabolic pathways are saturable
- HALF LIFE DOES NOT APPLY; it is NOT constant
- ex: phenytoin, ethanol, aspirin, heparin, theophylline, warfarin
Define dose-dependent elimination.
For drugs that are eliminated primarily by metabolism...
- concentration > Km = zero order; C/t = Vmax
Define total clearance.
sum of clearance by all eliminating organs and tissues
Define elimination half life.
T1/2 = 0.69xVd/CL ====> k = CL/Vd
time it takes to eliminate 50% of the drug
What are the 2 primary pharmacokinetic factors?
How do you determine time it takes to reach steady state?
t0.90 = 3.3t0.50
Why do you adjust for renal insufficiency? How can you adjust?
- impaired clearance of drugs eliminated by the kidneys
- daily dose must be reduced to prevent buildup of drug and toxic concentration levels
- adjust by reduced dose or increased dose intervals or both
Define creatinine clearance rate.
CrCL = volume of blood plasma that is cleared of creatinine/time
- used to approximate GFR
- measures kidney function
- used to adjust dosage for renal failure
List determinants of hepatic clearance.
1. hepatic blood flow - rate of drug delivery to liver
2. plasma protein binding - fraction of drug available for clearance
3. intrinsic clearance - hepatocellular metabolism and bile excretion
Define restrictive hepatic clearance.
- for drugs that are not extracted by the liver
- blood flow does not matter in the equation (Q >> fxCL)
- CLh = fxCLint
- aka capacity-limited
- ex: warfarin, phenytoin