Bioequivalence and Bioavailability Forum

Dear Muneesh,

I am going to try to answer your questions. Any other observations from experts will be welcome!

❝ 1. Does half-life of a drug change if we do a study in healthy subjects in

❝ fasting/fed state?

Fasting and Fed studies are applied to evaluate the absorption and/or bioavailability of drugs. So, the half-life of a drug is not changed in these conditions since this parameter isn't dependent of absorption. Half-life is dependent of volume of distribution and clearance (t_1/2 = 0.693 x V_d/CL)

❝ 2. Does half-life of a drug change if we do a study in healthy subjects

❝ after a single dose/at steady state following a multiple dose?

The half-life can be changed if a drug is administered in single or multiple doses. After multiple doses the metabolism of the drug may be saturated and the half-life may be changed (lower clearance, so higher t_1/2 considering: t_1/2 = 0.693 x V_d/CL). For example, amiodarone has a half-life of 600h after multiple dose and 50h after single dose.

❝ 3. Does half-life of a drug change if administered by different route e.g.

❝ IV, oral, inhalational, intranasal or any other route?

The half-life is dependent of V_d and CL. Different routes of administration may change the bioavailability of the drug, but not the half-life value.

❝ Because If I'm planning to do a BA study on inhaler or nasal spray, and

❝ the literature gives half-life of that drug after IV administeration only.

❝ In that case,is the half-life of that drug remains same for

❝ inhalational/intranasal route?

In my opinion you may use the IV data to design your study.

Regards,

Daniel Rossi de Campos

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Edit: Standard quotes restored. [Helmut]