prof. flavia franconi university of sassari. pharmacogenetics chronopharlacology pharmacogenetics...

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Prof. Flavia Franconi University of Sassari

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Page 1: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

Prof. Flavia Franconi

University of Sassari

Page 2: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators
Page 3: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

  

Pharmacogenetics chronopharlacology

 

    

 

Pharmacogenetics chronopharlacology

Drugs

Pharmacokinetics Modulators of pharmacological effects (sex hormones)

Pharmacodynamics

Efficacy and Safety

Modulators of pharmacological effects (sex hormones)

Page 4: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

The presence of critical periods

The wide use of oral anticonceptionals creates another population to be studied

Page 5: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

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).

Page 6: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

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

Page 7: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

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,

Page 8: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

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).

Page 9: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

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

Lactation

Page 10: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

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].

Page 11: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

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)

Page 12: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

Neonatal treatment has different long lasting effect in males and females

Page 13: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

Psychosocial Nutrition Drug/

ChemicalsIllness Physical

INFANT

Event induced response

ADULTSCardiovascular diseases, DM, obesity, behaviour

Page 14: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

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 largelyunderstudied. (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 ).

Page 15: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

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.

Page 16: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

it is important to know the transferability of results to humans

Page 17: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators

Gender Pharmacology

Individuate GD

Individuate them in the

single period of life

Use the biodiversity to improve the health