If the intravenous dose is kept very low but the oral dose is administered at a therapeutically relevant level, how do you know that the plasma pharmacokinetics will be linear between the doses?
There are no issues of dose proportional pharmacokinetics in the IVPK study design. The drug concentration in plasma is determined overwhelmingly by the absorption of the extravascular dose (typically oral). The elimination pharmacokinetics of the intravenous dose are determined by the total drug concentration present in the plasma, which, as stated above, is driven by the oral dose. The technique was originally developed in the 1970’s using stable isotope tracers to eliminate potential dose dependent clearance effects that can occur when the intravenous and oral doses are given separately in a traditional absolute bioavailability study design. There were problems with the assay sensitivity using stable isotopes but this is eliminated using a rare isotope such as 14C and Accelerator Mass Spectrometry. The pharmacokinetics and values for absolute bioavailability are actually more reliable using the IVPK design than a traditional cross-over type study.
Related Questions
- If the intravenous dose is kept very low but the oral dose is administered at a therapeutically relevant level, how do you know that the plasma pharmacokinetics will be linear between the doses?
- Rather than saying the intravenous dose is given simultaneously with the oral dose, it is often stated that the intravenous dose is given concomitantly -what does this mean?
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