| Indication |
For the treatment and prevention of osteoporosis in women and Paget's disease of bone in both men and women. |
| Pharmacodynamics |
Alendronate, a second-generation bisphosphonate is the first
member of a group of drugs which strengthens bone. Alendronate is used
to reduce hypercalcemia in tumor-induced bone disease, to treat
corticosteroid-induced osteoporosis and Paget's disease, and to prevent
osteoporosis in postmenopausal women. |
| Mechanism of action |
The action of Alendronate on bone tissue is based partly on its
affinity for hydroxyapatite, which is part of the mineral matrix of
bone. Alendronate also targets farnesyl pyrophosphate (FPP) synthase.
Nitrogen-containing bisphosphonates (such as pamidronate, alendronate,
risedronate, ibandronate and zoledronate) appear to act as analogues of
isoprenoid diphosphate lipids, thereby inhibiting 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 |
Relative to an intravenous (IV) reference dose, the mean oral
bioavailability of alendronate in women was 0.7% for doses ranging from 5
to 40 mg when administered after an overnight fast and two hours before
a standardized breakfast. Oral bioavailability of the 10 mg tablet in
men (0.59%) was similar to that in women (0.78%) when administered after
an overnight fast and 2 hours before breakfast. |
| Volume of distribution |
|
| Protein binding |
78% |
| Metabolism |
There is no evidence that alendronate is metabolized in humans or animals. |
| Route of elimination |
Following a single IV dose of [14C]alendronate, approximately 50%
of the radioactivity was excreted in the urine within 72 hours and
little or no radioactivity was recovered in the feces. |
| Half life |
>10 years |
| Clearance |
- <200 mL/min [A single 10 mg IV dose]
|
| Toxicity |
Alendronate can damage the esophagus both by toxicity from the
medication itself and by nonspecific irritation secondary to contact
between the pill and the esophageal mucosa, similar to other cases of
"pill esophagitis." |
