PMID- 11488556
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20170214
IS  - 1091-5818 (Print)
IS  - 1091-5818 (Linking)
VI  - 20
IP  - 3
DP  - 2001 May-Jun
TI  - Gender-based differences in the toxicity of pharmaceuticals--the Food and Drug 
      Administration's perspective.
PG  - 149-52
AB  - Women experience more adverse reactions to treatment with therapeutic drugs than 
      men. Theories proposed to explain this include overdosing, different 
      pharmacokinetics and pharmacodynamics, women are more likely to report adverse 
      events than men, or women take more medications than men. Food and Drug 
      Administration (FDA) Office of Women's Health (OWH) funds research to promote 
      including women in clinical trials and understanding the biology of sex-related 
      differences in the safety of FDA-regulated products. Including women in clinical 
      trials advances the understanding of drug efficacy and safety in women by 
      providing information on drug dosing, pharmacokinetics, and pharmacodynamics. A 
      Baysian statistical analysis of sex differences in adverse events showed that 
      although about the same number of adverse events were reported for men and women, 
      those reported for women were more serious. One example of a sex difference in 
      the toxicity of pharmaceuticals is the drug-induced cardiac arrhythmia, torsades 
      de point. OWH funded studies in animals and humans to investigate the mechanism 
      behind this sex difference. These studies demonstrated that shortening the QT 
      interval increases the risk of developing torsades and that androgens protect 
      against torsades by slowing cardiac repolarization and prolonging the QT 
      interval. Understanding the mechanisms behind other reported sex-related 
      differences in adverse drug effects requires additional research. The preliminary 
      studies conducted to date suggest that this sex-related difference is likely to 
      be a multifactorial problem requiring information from several fields of study. 
      Ideally, individuals at risk for developing an adverse event should be identified 
      prior to therapeutic intervention. The OWH plans to fund more studies to 
      investigate the role of hormonal variations on drug metabolism and drug-drug 
      interactions. Animal and in vitro model systems are needed to fully understand 
      the mechanism of how gender influences drug toxicity.
FAU - Miller, M A
AU  - Miller MA
AD  - Office of Women's Health, Food and Drug Administration, Rockville, Maryland 
      20857, USA. MMILLER1@OC.FDA.GOV
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Int J Toxicol
JT  - International journal of toxicology
JID - 9708436
RN  - 0 (Androgens)
SB  - IM
MH  - Androgens/pharmacology
MH  - Animals
MH  - Clinical Trials as Topic
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Health Policy
MH  - Humans
MH  - Research Design
MH  - Risk Factors
MH  - Sex Factors
MH  - Torsades de Pointes/*chemically induced
MH  - United States
MH  - United States Food and Drug Administration
MH  - *Women's Health
EDAT- 2001/08/08 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/08/08 10:00
PHST- 2001/08/08 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/08/08 10:00 [entrez]
AID - 10.1080/109158101317097728 [doi]
PST - ppublish
SO  - Int J Toxicol. 2001 May-Jun;20(3):149-52. doi: 10.1080/109158101317097728.