1-45 PHarmacokinectics Quantitative Flashcards
Bioavailability (F)
fraction of the administered dose that is reached the systemic circulation, dependent on protperties of the drug IV drugs: F=1 Non IV drugs: F<1 Measure of extent not rate of absorption
slope of oral and of IV should be the same after processing
what does extra-vascular drug distribution look like on graph?
Volume of distribution equation
- Vd (Liters) = Dose of drug (mg) / [drug] (mg/L)
- Volume of fluid required to contain all the drug in the body at the same concentration as in plasma
- the extenet of drug distirbution to extravascular tissues: not a physicial volume, “apparent” volume
- Not known at time of dosing, average value that is assumed
- Clinical utility: to etablish therapeutic [plasma] rapidly
- Low values: 7-8L
- happenes if bound by protein the vascular space
- High values: hundred of L
Plasma protein binding
- albumin
- only free drug is active
- low <20%
- High >95%
- High plasma protein biding = low Vd
Clearance (CL) of drugs
-
Clearance: Volume of plasma that get cleared of drug per unit time
- Liter/hour or mL/minute (normalized by BW)
-
Rate of elimination = amount of drug removed per unit time
- mg/hour
- Rate of elimination = CL x [plasma]
- Continuous infusion
- [Plasma] = K0(infusion rate of drug)/CL
- Oral doses
- [Plasma]=Fx(D/t)/CL
- Clearance-total= sum of all organs doing their indiviudal clearances
- This helps with rate of dosing to achieve therapeutic effect
- Rate of elimination is directly proprotional to concentration (first order metabolism) so clearance remains the same!
Clearance of drugs for first order metabolism
Rate of elimination is directly proprotional to concentration (first order metabolism) so clearance remains the same!
1st order and 0 order rate of elimination
half life
- t1/2 = 0.693 x Vd / Clearance
- indepedent of clearance (which usually stays the same)
- volume of distribution and clearance are also independent
- half life should also remain same if first order
- if rate of elimination is capped (kidney fail or something) then the half life will be different depending on drug dose, clearance will be changing constantly with the dose of the drug
Linear vs. Nonlinear pharmacokinetics
- Linear: t1/2 constant, clearance constant, will increase the rate of elimination proprotionally
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Steady State of Drugs, Css
(Steady State Concentration, for continuous infusion) Css = infusion rate (amount/time) / Clearance
Css (for repeated dosing) = dose (mg) / dosing interval x CL
Clearnace needs to balance infusion rate to hit the goal plateau that we want the drug at, may require several doses
if dose have a changed bioavailability, then you need to correct the dose (multiply and dose higher)
3.3 half-lives to reach 90% Css
we like to dose a drug every half life to get to Css
Dosing interval / TI
- dosing interval becomes critical for drugs like this
- more frequent dosing, less high/lows
- less frequent dosing, greater range in plasma
Loading and maintencance dose
- Plasma [drug] decreases intitially due to distirbution
- Significant for drugs with high Vd (weight, sex, age can alter your Vd)
- Css not reached promptly so we shoot for the Css on the loading dose and then try to give maintence dose to keep in therapeutic window
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Loading dose = Vd x Css
- larger the Vd larger the LD
- Affect by factors that influence Vd (afe, weight, sex)
- Maintenance dose: CL x Css
Pharmacokinectics key points