Pharmacokinetics and Pharmacodynamics Flashcards
(12 cards)
Define halflife.
Half life (t1/2): empirically determined from a single i.v. dose as the time for the plasma concentration to fall by 50%. (units are hr or min)
Pharmacokinetics
What is the equation for the constant for drug elimination?
In practice, once you know the half-life you can then determine the time Konstant for drug elimination (Kel):
Kel = 0.693 ÷ t1/2 (hr-1 or min-1)
where 0.693 is the value of ln(2), i.e. the decrease in drug is logarithmic and you are focusing on a 2-fold change in concentration
What is the meaning of the constant for drug elimination
Kel is the rate of decay at t = 0 (relative to the starting drug concentration, C0). Since first order decay has an initial ~linear phase, Kel can be use to accurately estimate plasma levels early in the decay when t ≤ (t1/2 ÷ 2).
What is the equation for determining remaining drug concentration?
C,t =(halflife/2) ≈ C0 – (C0 x Kel x t)
What are the equations for half-life?
t1/2 = 0.693 ÷ Kel (hr or min)
= 0.693 x (Vd ÷ Clp) (hr or min)
What is the volume of distribution? What is the equation?
Volume of distribution (Vd) is empirically determined and is the apparent volume in which a drug is distributed. It is not an “anatomical value” but instead reflects the various body compartments that the drug can rapidly access. Vd is determined from the initial plasma concentration (C0, in mg/L), which is measured immediately after a single i.v. dose (D, in mg) has rapidly equilibrated between plasma and the surrounding tissues:
Vd = D ÷ C0 (L)
In many cases a Vd will be adjusted for body weight (unadjusted Vd ÷ body weight) so you may also see Vd. expressed as L/kg.
What is plasma clearance? What is the equation?
is the volume of plasma cleared of drug per unit time. This is dependent on the half-life (from which you can calculate Kel) and the volume of distribution:
Clp = Kel x Vd (L/hr or L/hr/kg)
The final units will depend on the units of Vd. Final units are L/hr for unadjusted Vd and L/hr/kg for body weight adjusted Vd.
What is the maintenance dose? What are the equations for it?
Maintenance Dose (MD) is the dose at a specified dosing-interval required to achieve a specific steady state concentration (CSS). Recall, the plasma concentration of a drug is dependent on the amount of drug administered, the frequency of administration and the half-life of the drug. If you give a fixed amount of drug at fixed intervals then you will achieve steady state concentration after about 4 half-lives (4 x t1/2). So MD can be determined from either Kel or Clp, which are both derived from t1/2:
MD = Css x Vd x Kel x dosing-interval
= Css x Clp x dosing-interval
What are the pharmacodynamic equations where bigger is better?
Therapeutic Index (TI) = LD50 ÷ ED50
Margin of Safety Index (MI) = LD1 ÷ ED99
Protective Index (PI) = ED50(undesirable) ÷ ED50(desirable)
What are the pharmacodynamic equations where smaller is better?
Chronicity Index (CI) = one-dose LD50 ÷ ninety-dose LD50
What is the loading dose? What is the equation?
is the dose required to “instantly” achieve a steady state concentration (Css):
D* = Css x Vd (mg or mg/kg)
What is the oral fraction? What is the equation for the oral fraction?
Oral Fraction (Foral) or bioavailability is total amount of drug that enters the plasma from oral administration vs. i.v. administration. Determined by integrating graphs for plasma concentration vs. time i.e. the “area under the curve (AUC)”: Foral = AUCoral ÷ AUCi.v. (0.0 - 1.0) The higher the Foral the greater the bioavailability.
