Ostivea Mechanism of Action

Pharmacology: Pharmacodynamics: The pharmacodynamic action of ibandronic acid is inhibition of bone resorption. In vivo, ibandronic acid prevents experimentally induced bone destruction caused by cessation of gonadal function, retinoids, tumors or tumor extracts. In young (fast growing) rats, the endogenous bone resorption is also inhibited, leading to increased bone mass compared with untreated animals. The high potency and therapeutic margin of ibandronic acid allows for more flexible dosing regimens and intermittent treatment with long drug-free intervals at comparatively low doses. Both daily and intermittent (with prolonged dose-free intervals) long-term administration in rats, dogs and monkeys were associated with formation of new bone of normal quality and/or increased mechanical strength even in doses in excess of any pharmacologically intended dose, including the toxic range. In humans, the efficacy of both daily and intermittent administration with a dose-free interval of 9-10 weeks of ibandronic acid was confirmed, in which ibandronic acid demonstrated anti-fracture efficacy. Both daily and intermittent (with a drug-free interval of 9-10 weeks per quarter) oral doses as well as intravenous doses of (product name) in postmenopausal women produced biochemical changes indicative of dose-dependent inhibition of bone resorption. (product name) intravenous injection decreased levels of serum CTX within 3-7 days of starting treatment and decreased levels of osteocalcin within 3 months. Following treatment discontinuation, there is a reversion to the pathological pre-treatment rates of elevated bone resorption associated with postmenopausal osteoporosis. The histological analysis of bone biopsies after two and three years of treatment of postmenopausal women with doses of (product name) 2.5 mg daily and intermittent i.v. doses of up to 1 mg every 3 months showed bone of normal quality and no indication of a mineralisation defect.
Mechanism of Action: Ibandronic acid is a highly potent bisphosphonate belonging to the nitrogen-containing group of bisphosphonates, which act on bone tissue and specifically inhibit osteoclast activity. It does not interfere with osteoclast recruitment. The selective action of ibandronic acid on bone tissue is based on the high affinity of this compound for hydroxyapatite, which represents the mineral matrix of the bone. Ibandronic acid reduces bone resorption, with no direct effect on bone formation. In postmenopausal women, it reduces the elevated rate of bone turnover towards premenopausal levels, leading to a progressive net gain in bone mass. Daily or intermittent administration of ibandronic acid results in reduced bone resorption as reflected in reduced levels of serum and urinary biochemical markers of bone turnover, increased BMD and a decreased incidence of fractures.
Pharmacokinetics: The primary pharmacological effects of Ibandronic acid on bone are not directly related to actual plasma concentrations.
Plasma concentrations of Ibandronic acid increase in a dose-proportional manner after intravenous administration of 0.5 mg to 6 mg.
Absorption: Not applicable.
Distribution: After initial systemic exposure, Ibandronic acid rapidly binds to bone or is excreted into urine.
Biotransformation: There is no evidence that Ibandronic acid is metabolised in animals or humans.
Elimination: Ibandronic acid is removed from the circulation via bone and the remainder is eliminated unchanged by the kidney.
The range of observed apparent half-lives is broad, the apparent terminal half-life is generally in the range of 10-72 hours.
Total clearance of Ibandronic acid is low with average values in the range 84-160 ml/min. Renal clearance accounts for 50-60% of total clearance and is related to creatinine clearance. The difference between the apparent total and renal clearances is considered to reflect the uptake by bone.
The secretory pathway appears not to include known acidic or basic transport systems involved in the excretion of other active substances.
Pharmacokinetics in special clinical situations: Gender: Pharmacokinetics of ibandronic acid are similar in men and women.
Race: There is no evidence for any clinically relevant inter-ethnic differences between Asians and Caucasians in ibandronic acid disposition.
Patients with renal impairment: Renal clearance of ibandronic acid in patients with various degrees of renal impairment is linearly related to creatinine clearance (CLcr).
No dose adjustment is necessary for patients with mild or moderate renal impairment.
The pharmacokinetics of ibandronic acid in patients with end-stage renal disease was only assessed in a small number of patients managed by haemodialysis, therefore, the pharmacokinetics of ibandronic acid in the patients not undergoing haemodialysis is unknown.
Ibandronic acid is not recommended in patients with severe renal impairment after intravenous administration of 0.5 mg of ibandronic acid, total, renal, and non-renal clearances decreased by 67%, 77% and 50% respectively, in those with severe renal failure, but there was no reduction in tolerability associated with the increase in exposure.
Due to the limited data available, ibandronic acid should not be used in all patients with end-stage renal disease. The pharmacokinetics of ibandronic acid in patients with end-stage renal disease was only assessed in a small number of patients managed by haemodialysis, therefore, the pharmacokinetics of ibandronic acid in the patients not undergoing haemodialysis is unknown.
Patients with hepatic impairment: There are no pharmacokinetic data for ibandronic acid in patients who have hepatic impairment. The liver has no significant role in the clearance of ibandronic acid, which is not metabolised but is cleared by renal excretion and by uptake into bone. Therefore dose adjustment is not necessary in patients with hepatic impairment.
Elderly population: As renal function decreases with age, renal function is the only factor to take into consideration.
Paediatric population: There are no data on the use of ibandronic acid in patients less than 18 years old.