Gender Effects in Pharmacokinetics and Pharmacodynamics

Abstract

There are a number of examples of sex differences in drug pharmacokinetics and pharmacodynamics. Recent advances in the characterisation of specific isozymes involved in drug metabolism now allow for the preliminary identification of enzyme systems that are affected by sex. While current data are somewhat limited and not in complete agreement, the majority of studies show that apparent cytochrome P450 (CYP) 3A4 activity is higher in women than in men, whereas the activity of many other systems involved in drug metabolism may be higher in men than in women. Women and men also show different pharmacodynamic responses to a variety of drugs. While the clinical significance of these sex differences remains to be determined, we anticipate that they will be most important in the administration of drugs that have a narrow therapeutic range. In addition, sex differences in drug metabolism may be involved in the higher incidence of adverse reactions to drugs in women compared with men. Further research is needed to determine the scope and significance of these sex differences. Female-specific issues such as pregnancy, menopause, oral contraceptive use and menstruation may also have profound effects on drug metabolism. These effects can often be clinically important. Pregnancy may increase the elimination of antiepileptic agents, reducing their efficacy. Oral contraceptive use can interfere with the metabolism of many drugs and, conversely, certain drugs can impair contraceptive efficacy. More research is needed to determine the impact of menopause, hormone replacement and menstruation on drug therapy.

A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent‐onset rheumatoid arthritis

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Effects of Progesterone on Benzene Toxicity in Rats

“…Our results suggest that oestrogens influence benzene toxicity not involving CYP450 isoenzymes. These observations are supported by Harris et al (34) who suggested that only a few CYP450 isoenzymes associated with biotransformation of drugs are under oestrogenic control. Similar observations were found in rats treated with lindane (35).…”

Pattern of Adverse Drug Reactions in a Govt. District Headquarters Hospital in Tamilnadu, India

“…Female are more likely than men to interpret the discomfort that is caused. [17][18][19][20] In this study, 96.25% (n=77) of ADR was identified and reported by trained pharmacist and 3.75% (N=3) by the physician respectively, thus the advantage of the trained pharmacist in identifying ADR is due to their ward round participation, patient interview and careful monitoring of laboratory data of patients. Most of the patients experienced diarrhoea affecting the gastro-intestinal organ system which is also similar to the study by Suh DC et al 21 Murphy et al 8 and Biradar et al 22 reported that aminoglycoside and non-opioid analgesics were the most offending drugs.…”