| Indication |
For the treatment and prevention of osteoporosis in postmenopausal women. |
| Pharmacodynamics |
Ibandronate is a nitrogen-containing bisphosphonate in the same
class as alendronate and risedronate. Ibandronate inhibits
osteoclast-mediated bone resorption. All of the bisphosphonates prevent
the breakdown of bone by bone cells called osteoclasts. In persons who
are at high risk for osteoporosis, bisphosphonates not only result in
increased amounts of bone and bone strength, they also reduce the risk
of hip fractures and other bone fractures. |
| Mechanism of action |
The action of ibandronate on bone tissue is based partly on its
affinity for hydroxyapatite, which is part of the mineral matrix of
bone. Nitrogen-containing bisphosphonates (such as pamidronate,
alendronate, risedronate, ibandronate and zoledronate) appear to act as
analogues of isoprenoid diphosphate lipids, thereby inhibiting farnesyl
pyrophosphate (FPP) synthase, an enzyme in the mevalonate pathway.
Inhibition of this enzyme in osteoclasts prevents the biosynthesis of
isoprenoid lipids (FPP and GGPP) that are essential for the
post-translational farnesylation and geranylgeranylation of small GTPase
signalling proteins. This activity inhibits osteoclast activity and
reduces bone resorption and turnover. In postmenopausal women, it
reduces the elevated rate of bone turnover, leading to, on average, a
net gain in bone mass. |
| Absorption |
Poorly absorbed (mean bioavailability following a 2.5 mg oral dose
is about 0.6% compared to intravenous dosing). Absorption is impaired
by any kind of food or drink other than plain water. |
| Volume of distribution |
|
| Protein binding |
90.9 to 99.5% over an ibandronate concentration range of 2 to 10 ng/mL |
| Metabolism |
No evidence of ibandronate being metabolized in humans. |
| Route of elimination |
Ibandronate is eliminated by renal excretion. Unabsorbed ibandronate is eliminated unchanged in the feces. |
| Half life |
10-60 hours |
| Clearance |
- 84 to 160 mL/min [IV administration]
|
| Toxicity |
LD50 = 811 mg/kg (rat, oral), side effects include bronchitis, pneumonia and urinary tract infections. |
