Gender differences in pharmacokinetics

Abstract

There is growing awareness that the underrepresentation of women in clinical trials and in particular in phase I studies may lead to incorrect handling of drugs. Despite the fact that investigations are not informed in a systematic way, there are a number of examples showing pharmacokinetic differences between gender. From the data actually presented, it can be concluded that the activity of CYP 3A4 activity as measured by elimination in vivo is higher in women compared to men. CYP isoenzymes other than CYP 3A4 seem to be more active in men than in woman, as are conjugation reactions, such as glucuronidation. The influence of changing hormonal levels during the lifetime of a woman has been looked at in some drugs but deserves further systematic investigation. The use of oral contraceptives can interfere with the metabolism of many drugs whereas, in pregnancy, the elimination of antiepileptics is increased which, without dose adjustment, leads to an increased number of seizures. The impacts of hormonal replacement therapy (HRT) on the pharmacokinetics of concomitantly given drugs is an important issue, as HRT is increasingly used, but more research is needed in this field.

Lopinavir/Ritonavir Pharmacokinetic Profile: Impact of Sex and Other Covariates Following a Change From Twice‐Daily to Once‐Daily Therapy

“…There has been a growing concern that this may have led to an incomplete understanding of the optimal dosing of ARV for female patients. 12 Existing data on the influence of sex on the PK profile of LPV consist primarily of abstracts presented in scientific meetings and were generated from retrospective database analyses. In a report by Bertz and colleagues, 13 LPV/r PK data obtained from a meta-analysis of 7 single-dose SGC bioavailability studies in healthy adults (144 males, 50 females) were analyzed.…”

“…An observed dose of LPV/r (800/200 mg) and background NRTIs were administered with standard breakfast containing 500 to 682 kcal, with 23% to 25% of calories from fat. Serial blood samplings at 0, 1, 2, 3, 4,6,8,12,16,20, and 24 hours postdose were performed. Blood samples were kept on ice until processed (within 60 minutes of collection).…”

Gender Differences in the Membrane Transport of Endogenous and Exogenous Compounds

“…The enzyme, cytochrome P-450 3A4 (CYP 3A4) is involved in the metabolism of over 50% of drugs in clinical use including erythromycin, lidocaine, and midazolam and is also responsible for the hydroxylation of steroid hormones. The activity of CYP 3A4 in women is 1.4 times greater than that in men (Harris et al, 1995;Gleiter and Gundert-Remy, 1996). Conjugation reactions also demonstrate gender-related differences.…”

Sex differences in the toxicity of polyethylene glycol-coated gold nanoparticles in mice

“…38 An obvious significant sex difference is physiological change during the menstrual cycle, as well as changes in plasma protein and hormonal levels. 39 These elements can cause possible effects on interactions between blood plasma and NPs, and thus induce different physiological responses during blood circulation for males and females. Therefore, sex differences result in possible toxicological differences, eg, reproductive system and liver injury.…”