1 - Exponential equations for calculating plasma levels after drug dosage
a. General
b. Intravenous one compartment
c. Intravenous multicompartment
d. Oral dose single compartment
e. Oral dose two compartment
Where C is the concentration at time (t); Ci is the respective exponential coefficient; -λi is the respective exponential constant
2 - Calculation of area under the plasma level versus time curve (AUC)
a. General
b. Intravenous multicompartment
c. Oral single compartment
3 - General calculation of area under the first moment curve (AUMC)
4 - Calculation of clearance (Cl)
a. From plasma or blood concentration versus time curves
Where F is the fraction of bioavailablity and is equal to 1 for an intravenous dose
b. From intrinsic clearance (Clint), blood flow to the eliminating organ (Q) and unbound fraction (fu) using the well-stirred mode
5 - Calculation of renal clearance (ClR)
Where is the amount excreted in urine between time t1 and t2 and is the area under the curve for the same time interval
6 - Clearance is additive
7 - Useful derivations using clearance or AUC
a. At steady-state
Where is the average steady-state plasma/blood concentrationb.Maximum bioavailability potential determined from intravenous dosing using hepatic extraction ratio (ER)but
Maximum bioavailability potential determined from oral dosing assuming loss
c.by hepatic extractiond. Absolute bioavailability (F)
e. Relative bioavailability (Frel)
8 - Volume of distribution calculated from an intravenous dose (V/F if calculated from other routes of administration)
a. Initial distribution volume (Vi) for bolus dosing only
Where C0 is the concentration extrapolated to zero time
b. Volume of distribution based on area (Varea)
Where λz is the exponential constant for the terminal phase
c. Volume of distribution at steady-state (Vss) .d. Volume of distribution based on relative plasma and tissue bindingWhere Vp is the volume of plasma, VT is the extravascular volume including erythrocytes, fu is the unbound fraction in plasma and fuT is the unbound fraction in tissue
9 - Calculation of half-life (t1/2)
a. Directly from plasma profilesb. From primary pharmacokinetic parameters
10 - Michaelis-Menton equation for enzyme kinetics
Where Vm is the maximum velocity, Km is the Michaelis-Menton constant and C is the total concentration of the sustrate. At low concentrations of the substrate (<< Km)
11 - Sigmoid Emax for receptor binding and pharmacological response
Where Emax is the maximum response, EC50 is the concentration at half the maximum response, C is the concentration and n is the Hill constant