Biomedical Engineering Reference
In-Depth Information
in man. The mean area under the curve (AUC) is 25
g h/mL.
Absolute bioavailability studies after intravenous administration
demonstrated 70-100 % in rabbits, dogs, and monkeys [
45
]. Intra-
venous administration of pegaptanib sodium causes the drug to
distribute mainly in plasma and not to peripheral tissues. In vivo
studies in rabbits with intravenous and intravitreal administration of
radiolabeled pegaptanib sodium were conducted. Intravenous
injections demonstrated highest radioactivity in kidneys, whereas
no radioactivity was detected in kidneys for animals receiving intra-
vitreal injection. In rabbits pegaptanib is excreted as a parent com-
pound, while the metabolites are primarily eliminated in urine [
45
].
Clinical trials with pegaptanib 0.3 mg exhibited statistically signifi-
cant benefits, at the end of one-year study.
μ
Adverse Reactions
: Ocular adverse events in the study groups
reported include anterior uveitis, blepharitis, conjunctivitis allergic,
corneal abrasion, corneal deposits, corneal erosion, diplopia,
endophthalmitis, eye inflammation, swelling, bleeding, eyelid
disorder, irritation, retinal artery spasm, retinal and vitreous hem-
orrhage, retinal scar, and retinal telangiectasia. In phase II clinical
trials subjects receiving 0.3 mg pegaptanib sodium had better visual
acuity outcomes with significant reduction in central retinal thick-
ness. These subjects are deemed to be less likely to need additional
therapy with follow-up photocoagulation [
46
].
4.2 Avastin
®
Indications and Usage
: Avastin (bevacizumab) is a recombinant
humanized monoclonal IgG1 antibody that binds and inhibits the
biological activity of VEGF similar to Macugen
®
.
Dosage and Administration
: Avastin
®
is an immunoglobulin (IgG)
composed of two identical light chains (214 amino acids and 453
residue heavy chains) containing N-linked oligosaccharide. It has a
molecular weight of approx. 149 kDa. The intravitreal dose is
empirically derived in comparison to molar concentrations of each
drug with 1.25 mg of bevacizumab being considered equivalent to
0.5 mg ranibizumab. The optimal dose frequency is not clear.
Clinical studies reported different dosing schedules with monthly
injection or as needed [
47
-
49
]. On an average, it is estimated that
six to nine injections in the first year and five injections in the
second year for each eye are required. Some patients may even
require injections in both eyes [
50
].
Drug Composition
: The monoclonal antibody is supplied at a con-
centration of 100 mg/4 mL or 400 mg/16 mL. These concen-
trated drug products are further diluted in 0.9 % saline solution
to achieve a concentration of 1.25 mg for intravitreal injection.
The entire procedure is recommended to be conducted under
aseptic conditions. Currently, prefilled syringes are available that
need to be used within 4-6 weeks.
