Stuff I Learned: D001x Medicinal Chemistry IX
Total clearance = hepatic clearance + renal clearance
Also clearance depends on blood flow (Q) and extraction ratio (E)
Therefore total clearance = Qh*Eh + Qr*Er
Volume of Distribution (Vd)
Apparent volume of plasma required to contain drug in plasma
An average 70kg man has 2.7L of plasma but Vd is often much larger than 2.7L (plasma volume is 0.039L/kg) because in reality drugs redistribute to peripheral compartment
Since concentration = amount/volume and the amount and Vd of a drug is known, the concentration can be determined. Then that concentration can be used with plasma volume to determine how much of the drug is actually in the central compartment
E.g. 25mg of ranitidine is given, Vd = 1.4L/kg = 98L in a 70kg man
Since plasma volume is 2.7L:
0.255mg/L = amount of drug in plasma / 2.7L
Amount of drug in plasma = 2.7L * 0.255mg/L = 0.69mg
Therefore, only 0.69mg of 25mg ranitidine given is in plasma
A higher % of protein binding decreases clearance and decreases Vd
However, half life and kel (elimination constant) remain the same
Drug concentration decreases sharply during the distribution phase, then more slowly during the elimination phase (though both happen together)
The end of the distribution phase is when concentration in tissues (Ct) reaches maximum and Vss (steady state volume) is reached
The equation for the blue line is represented by the equations (A and alpha representing distribution phase and B and beta representing elimination phase, in which alpha is usually larger than beta)
