[Action of drugs in relation to the administration route]

The factors capable of modifying the activity of a given drug may be divided into two categories: those related to the patient (age, sex, weight, state of health, genetic factors, etc.) and those related to the drug (pharmaceutical formulation, dose, dose frequency, interaction with other drugs taken more or less simultaneously and administration mode). One example of a drug whose action varies according to the mode of administration adopted is offered by the estrogens which may be given orally (estradiol valerianate, estriol, conjugated estrogens, etc.) or parenterally (estradiol valerianate intramuscularly; conjugated estrogens and estriol vaginally, estradiol as a skin gel, by subcutaneous implant or transdermally). Blood concentrations of estradiol and estrogen after the same dose vary considerably according to the administration mode adopted so that doses may have to be adjusted in order to achieve the same levels of the circulating hormone. Having no first pass effect on the liver, parenteral administrations have less influence than oral ones on the synthesis of certain proteins by the liver (increased SHBG, CBG, TBG, transferrin, ceruloplasmin, angiotensinogen, clotting factors VII, IX, X and X complex; decreased antithrombin III and anti Xa) and on lipid metabolism (increased biliary cholesterol, triglycerides and HDL, especially HDL2; reduced LDL). In particular, it has been found that estradiol (differently from other estrogens) when administered transdermically is able to relieve menopausal symptoms at doses which do not influence the liver synthesis of proteins.