Biomedical Engineering Reference
In-Depth Information
Figure
4.13. IMprophylaxis in cotton rats bymotavizumab-enriched glycoforms. (See the insert
for color representation of this figure.)
PK in in vivo model. Glycoforms are effective in binding to the RSV, and the
glycoforms remain in both the serum and lungs at concentrations necessary for viral
neutralization.
Overall, the nonclinical in vivo studies show that oligosaccharides are not required
for inhibition of RSV infection, and the variations in glycoforms do not affect pharma-
cokinetics and prophylaxis.
C
LINICAL
S
TUDIES
. Variations in glycoform distribution may have a potential impact
on the PK properties of themolecule. For example, an increased rate of clearance (shorter
half-life) for a drug molecule results in decreased exposure of the drug to the target and
therefore potentially a decrease in efficacy. Conversely, a decreased rate of clearance
(longer half-life) increases exposure, which can increase the risk to safety if there are
adverse effects of the drug. We evaluated whether variations in glycoform distribution
could affect PK properties of motavizumab and palivizumab.
Analyses were carried out to assess the effect of glycoform distribution on the
clinical PK parameter, area under the curve (AUC), as a measure of exposure. This
evaluation was based on a statistical modeling approach for clinical serum data from
palivizumab andmotavizumab lots used in clinical studies. The data sets for palivizumab
and motavizumab were considered together to determine the effect on PK because of the
following reasons:
Similar Amino Acid Sequences: There are 13 amino acid differences between
motavizumab and palivizumab, and all are in the Fab region (Fig. 4.14) [5].
.
Same Glycoforms: The structures of the glycoforms are the same but the
proportions differ (Fig. 4.15).
.
