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Francisco PereiraFrancisco de Matos Afonso Pereira received his degree in Pharmacy from the Faculty of Pharmacy of the University of Coimbra in Portugal in 2010 and is currently in the last year of his Ph.D. Studies at the UCL School of Pharmacy, London, UK.

Polyethylene glycol 400 (PEG 400) is reported as an “inactive ingredient” in drug monographs. PEG 400 can be employed as a solubility enhancing excipient with the aim of improving the dissolution and subsequent bioavailability of poorly soluble drugs. However, recent human studies have called into question the inert nature of pharmaceutical excipients such as PEG 400. The osmotic nature of PEG 400 in the human gastrointestinal tract is well documented. However, it has been shown that low doses of PEG 400 have an enhancing effect on the oral bioavailability of BCS class III drugs in male but not female subjects.

There are known significant physiological differences between men and women that can affect their response to medication. The variability in pharmacokinetic and pharmacodynamics is influenced by many factors (genetics, disease, diet, physicochemical properties of the drug, and formulation characteristics), but sex is also a relevant marker of interindividual variability. Historically, researchers tended to use male subjects in clinical trials for a variety of reasons. But in 1993, the Food and Drug Administration (FDA) overturned a previous regulation, which excluded women from early-stage studies, and issued new guidelines in favor of equal representation of males and females in clinical trials. Nevertheless, despite the emphasis of the FDA on inclusion of women in clinical trials, some other more target-oriented regulations still exclude many women. Gender-specific analyses are required to detect gender differences in effects of pharmaceutical and non-pharmaceutical interventions, but they are seldom performed.

The Product Quality Research Institute (PQRI) highlighted some risks that could arise from the extension of biowaivers to BCS class III drugs, mainly the possible influence of excipients on intestinal transit and on drug permeability. Furthermore, the excipients listed on the FDA database of approved excipients include a maximum “dose” of excipient contained in a single given formulation. Therefore, excipients used within these limits should not have any effects on the rate nor extension of drug absorption.

Our recent findings with male and female rat models and PEG 400 call this into question. Some excipients thought safe to be used should be reconsidered or at least further investigated, taking into account not only fed or fasted state but also possible differences caused by both genders.

Afonso-Pereira will present the findings from his study Thursday, November 14 on the effect of excipients on the oral bioavailability of BCS class III drugs and gender differences. To read more about this exciting breakthrough, view his abstract no. R6301, through the 2013 AAPS Annual Meeting and Exposition MyAgenda Planner.