1. Prof. Flavia Franconi University of Sassari

3. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators of pharmacological effects (sex hormones) Pharmacodynamics Efficacy and Safety Modulators of pharmacological effects (sex hormones)

4. The presence of critical periods The wide use of oral anticonceptionals creates another population to be studied

5. However, pharmacokinetic differences do not necessarily result in different pharmacological responses. For example, women in the luteal phase are more sensitive to methylprednisolone (as measured by cortisol suppression test). However, since they eliminate this drug more quickly than men, the final response of methylprednisolone is similar in both sexes (Lew et al., 1993).

6. Correlation between circulating levels of estradiol and amygdalamopioid receptor binding during the follicular phase during the follicular phase of 10 healthy women. Pearson correlation: r520.75;P, 0.01 (Smith AR et al J Clin Endocrinol Metab 83, 4498–4505, 1998

7. Actually, it is not yet completely elucidated whether gender can influence specific organ metabolism. The topic is relevant,because in some tissues, including particular neuronal populations, CYP isoenzyme expression can be as high as, or higher than, in liver cells and can also display a higher sensitivity toward environmental inducers (Miksys and Tyndale, 2002). Indeed, variations in the activity of brain CYP enzymes can contribute tothe inter-individual changes in drug responses,

8. Several physiological parameters (plasma volume, sympathic and parasympathic systems) are varied in pregnancy. The activity of some CYP is also changed, moreover, CYP enzymes are also localized in placenta (Anderson, 2005).

9. The time required to recovery the pre-pregnant status after the delivery regarding drug and physiological responses. Lactation

10. Programming is well established through experimental and epidemiological studies [Hales C.N et al. Br Med J 303, 1019, 1991; Phillips DI Diabetlogia 39, 1119, 1996; Lithell HO et al Br Med J 312, 406, 1996; McCance et al DR Br Med J.308, 942, 1994; Phillips DI Diabetologia 37, 150, 1994; Phipps K et al Diabetologia 36, 225– 228].

11. IVH Prevention Trial demonstrated that indomethacin significantly decreased the incidence of IVH, prevented parenchymal hemorrhage, and was associated with higher verbal test scores at ages 3 to 8 years, although this protective effect of indomethacin on cognitive outcome seemed to be specific only to male subjects (Ment LR, Vohr B, Makuch RW, et al. Prevention of intraventricular hemorrhage by indomethacin in male preterm infants. J Pediatr. 2004;145:832–834)

12. Neonatal treatment has different long lasting effect in males and females

13. PsychosocialNutrition Drug/ Chemicals IllnessPhysical INFANT Event induced response ADULTS Cardiovascular diseases, DM, obesity, behaviour

14. The question whether female and male have differently to placebo /nocebo effects hardly received any attention and at the moment, the issue is still controversial and largely understudied. (Rickels, 1965; Wilcox et al., 1992; Compton et al, 2003; Saxon et al, 2001; Gear et al., 1999; Averbuch and Katzper, 2001; Mencke et al., 2004; Olofsen et al., 2005 ).

15. It will be important to have standard values for single urine plasma and blood parameters referred to male and female, strains, age and hormonal cycle.

16. it is important to know the transferability of results to humans