Errors in clearance estimation after bolus injection and arterial sampling: nonexistence of a central compartment

In conventional pharmacokinetics monotonic decreasing drug disposition curves are usually assumed after bolus injection. For arterial sampling starting about 1 min after dosing the resulting neglect of the initial concentration peak leads to a relative overestimation of clearance which may be approximated by the percentage of systemic drug extraction. This error can be avoided by administering the drug as a short-term infusion.