Prof.

Flavia Franconi

University of Sassari
 Drugs

Pharmacogenetics Modulators of
chronopharlacology Pharmacokinetics
pharmacological
effects (sex hormones)

Pharmacogenetics Modulators of
chronopharlacology Pharmacodynamics pharmacological effects
(sex hormones)

Efficacy and Safety

The presence of critical periods

The wide use of oral anticonceptionals creates another

population to be studied
 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).
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
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,
 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).
 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].
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)
Neonatal treatment has
different long lasting effect in
males and females
 Drug/
Psychosocial Nutrition Illness Physical
Chemicals

INFANT

Event induced response

Cardiovascular diseases, ADULTS

DM, obesity, behaviour
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 ).
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.
it is important to know the
transferability of results
to humans
 Gender
Pharmacology

Individuate Use the

them in the biodiversity
Individuate GD
single period to improve
of life the health