138 - Advanced Pharmacokinetics Flashcards
Basic aspects of pharmacokinetics
ADME Administration, absorption, distribution, metabolism, excretion
Equation describing renal clearance of drug
(drug concIN - drug concOUT)/drug concIN * blood flow Extraction ratio x blood flow
Renal clearance
Amount of blood from which drug is removed by kidneys per time (EG mL/minute) GFT + TS - TR
Maximal GFR
120mL/min
Maximal CLrenal
800mL/min
CL
Rate of elimination/concentration of drug
CLtotal
CLrenal + CLhepatic + CLother (CLtotal is additive)
Normal relationship between drug concentration in blood and elimination
Normally the higher the blood concentration, the greater the rate of elimination (first order elimination)
Simplest way to administer drug (pharmacologically)
IV injection
Distribution equilibrium
When drug behaves in the body as if it is in a single compartment
Elimination rate constant
NOT ELIMINATION RATE. Is a constant that affects rate of elimination, in conjunction with the concentration of drug in the body
Relationship between drug concentration in the body with time after administration
Exponential decline in concentration
Features of rapid IV administration with first order elimination 1 2 a 3 a
• Rapid rise • Drug has half life – Time taken for concentration to fall by 1/2 • Peak concentration (Cpeak) related to dose (X0) and Vd - Cpeak ~= X0/Vd
Short term i.v. infusion with rapid distribution and first order elimination 1 2 3 4 5
• K0 (infusion rate) - KX • K0 is rate at which new bolus is administered. • rate of accumulation decreases as concentration increases • peak not as high as for i.v.bolus • after infusion over, get elimination only (simple first order)
Common K0 for rapid infusion
Every half hour to a few hours
What are rapid infusions useful for?
Useful for drugs that show toxicity at concentration not much greater than concentration that produces therapeutic effect
*Appearance of graph of rapid infusion
*Appearance of a graph of long term IV infusion
What is steady-state concentration relative to?
K0/(VdK), eg K0/clearance rate Proportional to rate at which drug is cleared. The more quickly it is cleared, the lower the steady state concentration
Features of long term i.v. infusion with one compartment model and first order elimination 1 2 a
• At steady state, rate of infusion = rate of elimination • Css is proportional to infusion rate – easy to dial up a particular concentration
With long term i.v. infusion with one compartment model and first order elimination, what does rate of infusion equal
Rate of elimination at steady state
*Long term IV dosing versus multiple dosing
How often are most drugs given with multiple dosing regimes?
Every half life of drug. Gives a 2x difference between peak and trough of drug concentration at steady state.
Number of half-lives required for getting to steady state with multiple doses
~7 half lives
When might a loading dose be needed with a multiple-dosing regime?
If the patient needs to get to steady state very quickly, EG heart failure, antimicrobials for sepsis.
How is a loading dose administered?
Give loading dose to get concentration to roughly steady state, then continue infusion as you would with a normal multiple dose regime
How is a loading dose calculated?
Using volume of distribution
Process by which most orally-administered drugs are absorbed in GIT
Lipid solubility, crosses cell membranes (lipid diffusion). Some drugs can be actively-transported, but this is uncommon.
Oral administration with one compartment model and first order elimination
dX/dT = KaXa - KX Xa = amount of drug at absorption site eg. in small intestine Ka = absorption rate constant Rate of change of drug in body (dX/dT) is related to absorption rate and elimination rate
Features of oral administration with one compartment model and first order elimination 1 2 3
• Peak not as high as with i.v. – Some elimination during absorption plus • Not all drug might be absorbed • Some drug might undergo first pass hepatic metabolism
How can bioavailability be calculated?
AUCoral/AUCiv x 100 = bioavailability. AUC = amount of blood in bloodstream (area under curve, referring to an integral of concentration/time graph)
Types of injected administration routes that have a similar concentration/time curve to oral administration
Intramuscular, subcutaneous
