Mode of action testosterone enanthate vs cypionate – a highly nitrogen-containing bisphosphonate inhibitor of osteoclastic activity. It does not affect the process of replenishing the pool of osteoclasts. The selective action of testosterone enanthate vs cypionate on bone tissue due to the high affinity of this substance to hydroxyapatite, the mineral component of bone matrix.
testosterone enanthate vs cypionate inhibits bone resorption and has no direct effect on bone formation. In postmenopausal women reduces the increased bone turnover rate to the level of reproductive years, resulting in an overall progressive increase in bone mass.
In vivo testosterone enanthate vs cypionate prevents bone destruction caused by the blockade of gonadal function, retinoids, tumors and tumor extracts. Inhibits endogenous resorption in young (growing) rats that manifests a higher bone mass in comparison to intact animals.
There were no signs of impaired bone mineralization at doses more than 5000 times the dose for the treatment of osteoporosis.
High activity and therapeutic range provide the ability flexible dosing regimen and intermittent administration of the substance in relatively low doses, with a long period without treatment.
and the constant and intermittent (one 9-10-week break in the quarter) prolonged use of oral medication Bonviva in postmenopausal women is accompanied by a dose-dependent inhibition of bone resorption, including including decline rates splitting bone collagen (the concentration of deoxypyridinoline and cross-linked C- and N-telopeptide of type I collagen) in urine and serum, increased bone mineral density (BMD) and decrease the incidence of fractures.
After the cessation of treatment there is a return to the pre-treatment had increased bone resorption rate in postmenopausal osteoporosis.
Histological analysis of bone samples obtained after 2 and 3 years of treatment in menopausal women showed normal characteristics bone tissue and no evidence of impaired mineralization.
Daily treatment Bonviva drug within 3 years (randomized, double-blind, placebo-controlled, study MF4411) is accompanied by a statistically significant reduction in the incidence of confirmed radiographically and morphometric vertebral fractures by 62% and clinically confirmed vertebral fractures by 49%. The weakening of bone loss is accompanied by a significantly less pronounced decrease in the growth of the patients compared with placebo.
Prevention of fractures persisted for the duration of the study, and signs of fading effect over time absent.
Revealed a similar decrease in the relative risk of non-vertebral fractures by 69% in patients at high risk (BMD T ratio for hip <-3,0 SD). These data are consistent with the results of clinical studies with other bisphosphonates.
When Bonviva daily use for 3 years increases in lumbar spine BMD by 6.5% compared to baseline.
Biochemical markers of bone resorption (the concentration of C-terminal peptide of type I procollagen in urine ( CTX) and serum osteocalcin) are reduced to their level of reproductive age; the maximum reduction observed after 3-6 months of treatment. A month after the start of Bonviva 2.5 mg daily and 20 mg intermittently achieved a clinically significant reduction in biochemical markers of bone resorption by 50% and 78%, respectively; furthermore, a reduction in these parameters observed after a week of treatment. Clinically significant reduction in biochemical markers of bone resorption (urinary concentration of the CTX) was observed one month after the start of treatment.
The daily intake of 2.5 mg Bonviva for the prevention of postmenopausal osteoporosis (study MF4499) increases the average lumbar spine BMD by 1.9% compared with the original level. Regardless of the duration of menopause and the degree of the initial losses of the basic substance of bone tissue, use of Bonviva leads to significantly greater change in lumbar spine BMD. When applying Bonviva effect of treatment, defined as the increase in BMD from baseline observed in 70% of patients.
not revealed a direct dependence of the efficiency of testosterone enanthate vs cypionate on the concentration of substances in the blood plasma. A similar efficacy of testosterone enanthate vs cypionate was confirmed in the daily and intermittent mode of application, provided her the same total dose administered over the period of treatment.
after oral administration of testosterone enanthate vs cypionate is quickly absorbed in the upper gastrointestinal tract, the blood plasma concentration in a dose-dependent increases with increasing dose up to 50 mg. Time to maximum concentration TCmax 0,5-2 hours (about 1 hours) after administration of fasting, the absolute bioavailability of 0.6%. Suction disturbed while taking the drug with food or drinks (except pure water).Simultaneous eating reduces testosterone enanthate vs cypionate bioavailability of 90%. When receiving testosterone enanthate vs cypionate for 60 minutes before eating significant reduction in bioavailability is not observed. Food or fluid intake of less than 60 minutes after testosterone enanthate vs cypionate reduces the bioavailability and caused by it increase BMD.
After initial contact with the systemic circulation testosterone enanthate vs cypionate rapidly binds to bone or excreted in the urine. 40-50% of the amount of drug circulating in the blood is well into the bone tissue and accumulates therein. The apparent volume of distribution is the final 90 liters. Communication with plasma proteins 85%.
There is no evidence that testosterone enanthate vs cypionate is metabolized there.
40-50% of the delivered into the bloodstream orally communicate the dose in the bones, and the remainder is excreted unchanged by the kidneys. Nevsosavsheysya drug is excreted unchanged in the feces.T1 / 2 phase terminal 10-60 hours. The concentration of drug in blood after oral administration decreases rapidly and reaches 10% of the maximum after 8 hours.
The total clearance of testosterone enanthate vs cypionate is 84-160 ml / min. Renal clearance (60 mL / min in healthy postmenopausal women) is 50-60% of the clearance depends on the clearance of creatinine. The difference between the total and renal clearance reflects the capture substance in bone.
Pharmacokinetics in special patient groups
Bioavailability and pharmacokinetics of testosterone enanthate vs cypionate in men and women alike.
There were no clinically significant racial differences in the distribution of testosterone enanthate vs cypionate in patients of South European and Asian races. Regarding the Negroid race is not enough data.
Patients with renal impairment
Patients with renal impairment Renal clearance of testosterone enanthate vs cypionate is a linear function of creatinine clearance (CC). For patients with impaired renal function, mild or moderate (creatinine clearance> 30 ml / min) dose adjustment is required.
Patients with severe renal impairment (creatinine clearance <30 ml / min) receiving the drug at a dose of 10 mg orally for 21 day testosterone enanthate vs cypionate concentration in blood plasma in a 2-3 times higher than those with normal renal function (total clearance of 129 ml / min). In severe impaired renal function the total clearance of testosterone enanthate vs cypionate is reduced to 44 ml / min. However, increasing the concentration does not impair the systemic tolerability.
Patients with impaired liver function
data on the pharmacokinetics of testosterone enanthate vs cypionate in patients with impaired liver function no. The liver plays a significant role in the clearance of testosterone enanthate vs cypionate that is not metabolized, and eliminated via the kidneys and by capturing in the bone. Therefore, in patients with impaired hepatic function dose adjustment is not required. Since therapeutic concentrations of testosterone enanthate vs cypionate is weakly bound to plasma proteins (85%) it is likely that hypoproteinemia in severe liver disease does not result in a clinically significant increase in the free concentration of the substance in the blood.
Age is not an independent factor for the pharmacokinetic parameters studied. With age, the possible decline in renal function, which should be considered in elderly patients (see. Above section “Patients with impaired renal function”).
data on the use of Bonviva in patients younger than 18 years are not available.
Treatment and prevention of postmenopausal osteoporosis in women.
Hypersensitivity to testosterone enanthate vs cypionate or any subsidiary component of the drug.
Neskorrigirovannye hypocalcemia and disorders of mineral metabolism.
Age 18 years (no clinical experience), pregnancy, lactation.
Severe renal insufficiency – creatinine clearance <30 mL / min.
Pregnancy and lactation
in rats and rabbits treated with oral testosterone enanthate vs cypionate, no evidence of a direct teratogenic effects or embryotoxic; at a dose of drug in excess of the dose for humans is at least 35 times, an adverse effect on development in the F1 offspring rats were detected. Adverse effects of testosterone enanthate vs cypionate in reproductive toxicity studies in rats were the same as for all bisphosphonates -. Reducing the number of embryos, violation of labor process, increasing the frequency of visceral abnormalities (narrowing syndrome UPJ)
clinical experience with Bonviva in pregnant women do not have.
is displayed with the milk of rats. After 24 hours, testosterone enanthate vs cypionate concentrations in plasma and milk is the same and corresponds to 5% of the maximum.
It is not known whether output testosterone enanthate vs cypionate in breast milk of women.
Dosage and administration
Inside, 2.5 mg (1 tablet) once daily for 60 minutes prior to the first day of ingestion, liquids (other than water), or other drugs and food additives.
- The tablets should be swallowed whole with a glass (180-240 ml) of clean water in a sitting or standing, and did not stay up for 60 minutes after taking the drug Bonviva.
- Do not use mineral water, which contain a lot of calcium.
- Tablets should not be chewed or sucked due to the possible formation of esophageal ulcers.
Dosage in special patient groups
Abnormal liver function
No dose adjustment is required (see. Section Pharmacokinetics in special patient groups).
In a weak and moderately severe impaired renal function (creatinine clearance> 30 ml / min) dose adjustment is required. When creatinine clearance <30 mL / min, the decision to use the drug Bonviva should be based on an individual assessment of the risk-benefit ratio for the individual patient (see. Pharmacokinetics in special patient groups).
No dose adjustment is required.
Safety and efficacy in patients under the age of 18 years have not been established.
Side effects Gastrointestinal tract: dyspepsia, diarrhea, esophagitis, ulcer or stricture of the esophagus, gastritis, doudenit. Musculoskeletal System: myalgia, arthralgia. Skin and appendages: rash, urticaria.Nervous system: headache, dizziness. The body in whole: flu syndrome, fatigue, back pain, hypersensitivity reactions Laboratory indicators: reduction in alkaline phosphatase activity.
Symptoms: indigestion, heartburn, esophagitis, gastritis, ulcer, hypocalcemia, hypophosphatemia.
Treatment. Specific information is missing. To bind Bonviva used milk or antacids. Due to the risk of oesophageal irritation do not induce vomiting, and need to be rectified in a standing position.
Interaction with other drugs
Interaction with food
products containing calcium and other polyvalent cations (for example, aluminum, magnesium, iron), including milk and solid food, can interfere with the absorption of the drug, they should be used no earlier than 60 minutes after oral Bonviva drug.
Calcium supplements, antacids and medications containing polyvalent cations (such as aluminum, magnesium, iron) can interfere with the absorption of testosterone enanthate vs cypionate, so they should be taken no earlier than 60 minutes after taking Bonviva.
Bicfosfonaty and non-steroidal anti-inflammatory drugs ( NSAIDs) may cause irritation of the gastrointestinal tract. It should be particularly careful when using NSAIDs along with Bonviva.
In / in the introduction of ranitidine increases testosterone enanthate vs cypionate bioavailability of 20%, but does not require dose adjustment of the drug while the use of blockers H2-histamine receptors or other drugs that increase gastric pH.
testosterone enanthate vs cypionate does not affect the basic isoenzyme cytochrome P450 system. At therapeutic concentrations of testosterone enanthate vs cypionate is weakly bound to plasma proteins, and therefore, it is unlikely that it will displace from binding sites with proteins other medicines. testosterone enanthate vs cypionate is derived only through the kidneys and is not subject to any biotransformation. Apparently, testosterone enanthate vs cypionate removal path does not include any transport systems involved in the removal of other drugs.
Osteoporosis can be confirmed by detection of low bone density (T <2,0 SD) and / or by the presence of osteoporotic fracture (including history). Risk factors for postmenopausal osteoporosis and fractures: family history, transferred fractures, early menopause, active bone metabolism, low BMD (at least 1,0 SD below the average BMD of reproductive age), fragile body, as well as the South women European and Asian races, smoking. These factors are important in deciding on the appointment of Bonviva for the prevention of osteoporosis.
Prior to the use of Bonviva drug should be ‘corrected hypocalcemia and other disturbances of bone metabolism and electrolyte balance. Patients should consume enough calcium and vitamin D.
If a patient gets from food is not enough calcium and vitamin D should be added to take them in the form of food supplements. Using other bicfosfonatov often accompanied by swallowing, oesophagitis and the formation of esophageal ulcers and stomach, so it is necessary to pay special attention to the recommendations on the admission of the drug (sitting or standing for 60 minutes after administration, see section “Dosage”.).
If signs and symptoms of possible oesophageal lesions (new or worsening swallowing disorders, pain on swallowing, chest pain, heartburn) you should stop taking the drug Bonviva and seek medical advice.