Bioavailability study

Aim:

To determine the absolute or relative bioavailability of the test item.

Species:

Species used for preclinical R&D, no NHP.

Absolute bioavailability:

In life phase: Single intravenous and extravascular administration of the test item. For rats, if useful jugular vein cannulated model is used. Collection of blood/serum/plasma samples at scheduled time-points.

Bioanalysis: Quantification of the test item in the blood/serum/plasma samples by reliable bioanalytical method.

Evaluation: Determination of the pharmacokinetic parameters by Phoenix WinNonlin software and calculation of the absolute bioavailability: as ratio of the extravascular and intravenous total systemic exposure.

Relative bioavailability:

In life phase:

Single extravascular administration of the test item

with different doses of the same type of formulation (dose-dependency of exposure)
with different formulations at the same dose level (exposure for different formulations)
using different administration routes (comparison of administration routes)
using the same dosage form in fasted and fed animals (food effect).

Bioanalysis: Quantification of the test item in the blood/serum/plasma samples by reliable bioanalytical method.

Evaluation: Determination of the pharmacokinetic parameters by Phoenix WinNonlin software and calculation of the relative bioavailability as ratio of the total systemic exposures to evaluate the dose-dependency, formulation effect, effect of administration routes or food effect.

Collecting different matrices from the same animals (e.g. plasma and brain) the organ/plasma concentration ratios and the relative tissue/plasma bioavailability can be evaluated.