Absorption after ingestion desogestrel is rapidly and completely absorbed from the gastrointestinal tract and converted to etonogestrel. Maximum serum concentration is reached in about 1.5 hours after administration. Bioavailability is 62-81%. The distribution of etonogestrel is bound to serum albumin proviron dosage and globulin, sex hormone binding . Only 4.2% of the etonogestrel is present in serum as free steroid, 40-70% and specifically bind .Ethinylestradiol induced increase concentration influences the binding to serum proteins etonogestrel, increasing the fraction associated , and reducing the fraction bound to albumin. The apparent volume of distribution is 1.5 L / kg.
Metabolism etonogestrel completely metabolized by known pathways of steroid metabolism. The metabolic clearance rate from serum is about 2 ml / min / kg.Simultaneous use of ethinyl estradiol does not affect the pharmacokinetics of desogestrel. Elimination concentrations of etonogestrel reduced in two steps. The final stage is characterized by a half-life of about 30 hours desogestrel metabolites are excreted via the kidneys and intestines in a ratio of about 6:.. 4 Condition equilibrium Pharmacokinetics etonogestrel depends levels, which increases 3-fold under the influence ethinylestradiol. When desogestrel daily intake levels of etonogestrel in serum increased 2-3 fold, reaching an equilibrium state in the second half cycle of the pills. EthinylestradiolAbsorption After oral ethinyl estradiol is rapidly and completely absorbed from the gastrointestinal tract. Maximum serum concentrations achieved within 1-2 hours. The absolute bioavailability (presistemna result conjugation and first-pass metabolism) is about 60%. Distribution Ethinylestradiol has high nonspecific binding to serum albumin (about 98.5%) and cause an increase in serum concentrations .The apparent volume of distribution of about 5 l / kg. Metabolism Ethinylestradiol presistemnomu undergoes conjugation in the mucosa of the small intestine and in the liver. Ethinyl estradiol is metabolized primarily aromatic hydroxylation to form various hydroxylated and methylated metabolites that are present in the form of free metabolites and conjugates as glucuronides and sulfates. The metabolic clearance rate is about 5 ml / min / kg. Elimination Reduction ethinyl estradiol serum concentrations is biphasic, terminal half-life is about 24 hours Unchanged drug is not eliminated, ethinylestradiol metabolites are excreted in the urine and bile in a ratio of 4: 6.. The proviron dosage of metabolites is about 1 day. Terms of the equilibrium state of equilibrium concentration is achieved after 3-4 days of treatment, when the plasma concentration is 30-40% higher than the concentration after a single dose.
COCs should not be used if any of the conditions listed below.
If any of these conditions arise for the first time during use, should be discontinued immediately.
- Venous thrombosis (including deep vein thrombosis, pulmonary embolism), including: history.
- Arterial thrombosis (including myocardial infarction, stroke) or thrombosis precursors (including transient ischemic attack, angina pectoris), including: history.
- Detection of predisposition for venous or arterial thrombosis, including resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein deficiency of the S, hyperhomocysteinemia, and antiphospholipid antibodies.
- Migraine with focal neurological symptoms history.
- Diabetes mellitus with vascular disease.
- The presence of serious or multiple risk factors for venous or arterial thrombosis (including severe arterial hypertension with blood pressure ≥160 / 100 mm Hg .; see para. “Precautions”).
- Pancreatitis now or in history, accompanied by severe hypertriglyceridemia.
- Severe liver disease at present or in history (to normalize the function of the liver).
- Swelling of the liver in the present or in history (benign or malignant).
- Confirmed or suspected hormone-dependent cancers (for example, genital and breast).
- Bleeding from the vagina of unknown etiology.
- Confirmed or suspected pregnancy.
- The period of breastfeeding.
- Smoking women older than 35 years (more than 15 cigarettes per day).
- Hypersensitivity to the active substances or to any of the excipients proviron dosage .Carefully
- age over 35 years;
- dysfunctional family history (ie venous or arterial thromboembolism in siblings, sisters or parents at a relatively early age). If you suspect that a family history before making a decision on the use of any hormonal contraceptive a woman should go to a specialist for advice;
- obesity (body mass index greater than 30 kg / m2);
- prolonged immobilization, major surgery, surgery on the lower limbs, or severe injury. In these situations, it is recommended to stop using the product (for planned surgical procedures no later than 4 weeks before surgery) and not to resume their use within 2 weeks after complete remobilization;
- superficial thrombophlebitis, varicose veins;
- smoking (with increasing age and number of cigarettes smoked per day increases the risk, especially in women over 35 years old);
- arterial hypertension;
- valvular heart disease;
- atrial fibrillation;
- in non-breastfeeding postpartum women breast;
- diabetes without vascular lesions;
- systemic lupus erythematosus;
- hemolytic-uremic syndrome;
- chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis);
- sickle cell anemia;
- changes in biochemical parameters indicative of the likelihood of hereditary or acquired predisposition for venous or arterial thrombosis, including resistance of activated protein proviron dosage, hyperhomocysteinemia, antithrombin III deficiency, deficiency of protein C, protein deficiency of the S, antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant) ;
- hypertriglyceridemia (including family history);
- acute and chronic liver disease, includingcongenital hyperbilirubinemiato restore the biochemical parameters.