Bioequivalence and Bioavailability Forum

Dear Mr Constantinos,

Please follow Forum Policy, See here

❝ Does the position of a subject during administration of an investigational medicinal product significantly affect gastric emptying time?

Yes.
Quote from Scientific article by Christian Queckenberg & Uwe Fuhr, Influence of Posture on Pharmacokinetics, Eur J Clin Pharmacol (2009) 65:109–119

Postures which favour rapid gastric emptying (sitting, standing, recumbent right) accelerate the absorption of orally administered drugs. Consequently, these postures favour a shorter time to reach peak plasma drug concentration (tmax) and a higher maximum plasma drug concentration (Cmax) and—in the case of transient saturation of first-pass metabolism—total exposure (area under the concentration–time curve, AUC) in comparison to recumbent left and supine positions (e.g. nifedipine: AUC 30 and 38% higher in standing and right lateral position vs. left lateral position; Cmax 149 and 80% higher, respectively). The magnitude of these postural effects depends strongly on the nature and amount of liquids and food ingested before drug administration and is most pronounced in the fasting state and after administration with a nonnutrient liquid. Changes in splanchnic–hepatic blood flow (e.g. reduction of estimated hepatic perfusion by 37% in standing vs. supine position) may substantially affect the metabolism of orally administered drugs, especially of those with a high/saturable first-pass metabolism. For highly protein-bound drugs (e.g. phenytoin, imipramine), the total plasma concentration has been found to be approximately 10% higher in standing than lying subjects due to changes in plasma volume.

❝ Should a protocol describe, for example, that a volunteer should remain in an upright position for a specific time period after administration?

Yes. Postural restriction requirements and Post dosing posture restriction time period should be mentioned in the protocol.

❝ Is there a guideline addressing this issue?

Quote from Health Canada BE Guidance
"Physical activity and posture should be standardized as much as possible to limit effects on gastrointestinal blood flow and motility."

Quote from EMA's BE Guidance
"As the bioavailability of an active moiety from a dosage form could be dependent upon gastrointestinal transit times and regional blood flows, posture and physical activity may need to be standardised."