Skip to 0 minutes and 15 seconds Macromolecule binding also affects drug transport. For example, non-specific binding to albumin or lipoproteins.
Skip to 0 minutes and 28 seconds That could be specific binding proteins that are involved in the transport and regulation of therapeutic proteins.
Skip to 0 minutes and 39 seconds Protein binding may prolong circulation time by acting as a storage depot.
Skip to 0 minutes and 47 seconds For example, binding of growth hormone with plasma protein actually result in 10 times decrease in clearance. But this also reduces receptor interactions by about the same magnitude. So, therefore, there’s no net gain for this macromolecule binding.
Skip to 1 minute and 11 seconds Receptor binding is another way of transport. Now for small molecules, receptor binding is usually negligible compared with the total amount of drug in the system. But for large molecules or proteins, a substantial fraction of a small dose could be bound to the pharmacologic target and could significantly affect distribution. For proteins, limited distribution does not necessarily reflect insufficient tissue uptake because of the high binding specificity.
Skip to 1 minute and 55 seconds The receptor-mediated uptake in the bone marrow, in this example, for Nartograstim, it’s a recombinant GCSF actually result in therapeutic effective concentration. Again because the amount required for effect is relatively small, therefore the receptor-mediated uptake actually result in good enough concentration to bring about the pharmacological effect. So transport and the distribution for biologics. Let’s just quickly summarize it. Biologics are absorbed and transported by the lymphatic system into the vascular space. Equilibrium is established in time between the vascular space and the interstitial space via convection. A fraction of the dose could then migrate from the interstitial space into the intracellular space via endocytosis.
Skip to 3 minutes and 9 seconds And the intra distribution or intercellular distribution or receptor binding elicits the response and is then frequently followed by the elimination of the biologics.
Macromolecules are large molecules including carbohydrates, lipids, proteins, and nucleic acids. In this juncture, macromolecules refer to proteins such as albumin, globulin or lipoproteins. Biologics are transported through the lymphatic tissues into the vascular system, followed by distribution in the interstitium, and finally reaching the intracellular structure. Macromolecule binding may hinder the rate of distribution and transport, hence impeding the onset of pharmacological action. On the other hand, macromolecule may preserve the biologics from quick turnover and actually favor therapeutic effect. The manifestation of macromolecule binding is multifaceted and intriguing. So is the receptor binding, which not only leads to therapeutic response but also subsequent catalytic metabolism.
Macromolecule binding is largely non-specific, but there are bindings to specific proteins as well. Macromolecule binding may hinder the rate of distribution and transport, hence impeding the onset of action. On the other hand, macromolecule may preserve the biologics from quick turnover and actually favor therapeutic effect. Binding and complexation of growth hormone with plasma protein is an example. Receptor binding is specific by nature; it not only leads to pharmacological effect but could be followed by catalytic metabolism. In this regard, it is to be noted that limited uptake of Nartograstim is sufficient for target recognition because of high affinity. Several PK/PD aspects of macromolecule binding will be encapsulated.