“Drug administration through the intravenous route over a negligible period of time”
Administering a drug intravenously ensures that the entire dose enters the general circulation. Intravenous administration bypasses the absorption phase and the hepatic first-pass effect. Bioavailability is therefore complete. The drug is then distributed throughout the body and then eliminated by the liver and/or kidney.
Three parameters determine the drug concentration-time profile after administration of an iv bolus:
- Dose: with higher doses, the initial drug concentration is also higher, but its relative rate of decline remains identical.
- Volume of distribution: a larger Vd implies a lower initial drug plasma concentration, but also a longer half-life (t1/2).
- Clearance: greater clearance of the drug leads to a faster rate of decline in the drug plasma concentration, and a shorter half-life (t1/2).
An iv bolus injection ensures the rapid achievement of very high peak concentrations, as may be required for some drugs, but contra-indicated for others.
With an iv bolus administration the amount of drug delivery is precisely controlled.
Distribution phase (early phase): After entering the systemic circulation, the drug is distributed throughout the body. Distribution can determine an early rapid decline in plasma concentration.
Elimination phase (late phase): Once the drug in the plasma and tissues has reached equilibrium, the decline of plasma concentration is driven by elimination of the drug from the body.
Analysing the plasma concentration-time profile after an intravenous bolus injection is very useful to calculate the different parameters such as clearance (CL), half-life (t1/2) and volume of distribution (Vd) of a given drug.
The equation of the plasma concentration-time curve for a drug with a negligible distribution phase is:
C(0) = plasma drug concentration at time 0
extrapolated value = D/Vd
D = dose
λ = elimination constant rate = CL/Vd