Progress in the Consideration of Possible Sex Differences in Drug Interaction Studies.

BACKGROUND Anecdotal evidence suggests that there may be sex differences in Drug-drug Interactions (DDI) involving specific drugs. Regulators have provided general guidance for the inclusion of females in clinical studies. Some clinical studies have reported sex differences in the Pharmacokinetics (PK) of CYP3A4 substrates, suggesting that DDI involving CYP3A4 substrates could potentially show sex differences. OBJECTIVE The aim of this review was to investigate whether recent prospective DDI studies have included both sexes and whether there was evidence for the presence or absence of sex differences with the DDIs. METHODS The relevant details from 156 drug interaction studies within 124 papers were extracted and evaluated. RESULTS Only eight studies (five papers) compared the outcome of the DDI between males and females. The majority of the studies had only male volunteers. Five studies had females only while 60 had males only, with 7.7% of the studies having an equal proportion of both sexes. Surprisingly, four studies did not specify the sex of the subjects. Based on the limited number of studies comparing males and females, no specific trends or conclusions were evident. Sex differences in the interaction were reported between ketoconazole and midazolam as well as clarithromycin and midazolam. However, no sex difference was observed with the interaction between clarithromycin and triazolam or erythromycin and triazolam. No sex-related PK differences were observed with the interaction between ketoconazole and domperidone, although sex-related differences in QT prolongation were observed. CONCLUSION This review has shown that only limited progress had been made with the inclusion of both sexes in DDI studies.

• Publication year

  2019

• Venue

  Current drug metabolism

• Publication date

  Unknown publication date

• Fields of study

  Medicine

• Identifiers
  DOI 10.2174/1389200220666181128160813PMID 30488793
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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