Bioequivalence and Bioavailability Forum

Dear Raghu,

❝ If we give additional water during dosing to a single subject, will it affect the solubility of the product and subsequently on the absorption, pk and stats results. However it depends on the amount of water what we have given.

In fasted state such differences are unlikely. Non-caloric liquids are leaving the stomach within minutes (google for “Magenstrasse”).

❝ If it occurs in P-I, can we give the same amount of additional water to the same subject in next period(s) to avoid variability.

If you want to minimize any potential difference you can do that.

❝ Can we drop the subject from the study, to avoid the queries from the regulatory.

Wrong question. You should ask yourself whether there might be an impact based on scientific grounds. Anticipate such incidents and give a procedure to follow in the protocol. If you haven’t done so, consider performing a sensitivity analysis (with/without the subject) and discuss the potential impact on the BE assessment in the report. “Exlusion to avoid regulatory queries” IMHO is never a good justification.

See this presentation by Werner Weitschies:

Potential impact of excipients and size/shape of dosage form on GI transit
EUFEPS Conference, June 2008, Bad Homburg, Germany