Pharmacokinetics of Protein-based Drugs

Study Notes

Between 3000 and 10,000 new protein-based drug targets can be identified within the human genome sequence.
Hundreds of pathogen proteins present in human pathogens provide additional targets for drug development.
Genomics facilitates the discovery of previously unrecognized proteins with potential therapeutic applications.

Pharmacokinetics (PK) refers to how the body modifies drugs post-administration, differing significantly for peptides/proteins compared to traditional chemical drugs.
Chemical drugs are treated as exogenous molecules, leading to their elimination once recognized by the body.
Biotech drugs are not perceived as foreign, hence they are not expelled like conventional drugs; instead, they are digested and absorbed.
Administration of biotech drugs typically occurs via parenteral routes: intravenous, subcutaneous, and intramuscular due to their high molecular mass and instability in non-parenteral forms.

Only 1 in 1000 chemical drugs successfully reaches the final phase of drug discovery, whereas biological drugs progress more easily with known protein structures indicating function.
Biologics often exhibit improved specificity, reducing the risk of off-target side effects commonly linked to small molecules.

Key initial step in biotech drug production is gene cloning, such as producing insulin from A and B chains.
Essential knowledge for biotech drug development includes genomics, focusing on gene function and mutation analysis in various conditions.
Proteomics also plays a critical role in understanding protein function and structure, providing insights essential for drug development.

Biotech drugs can target either genes/products of transcription (gene therapy/antisense nucleotides) or gene products of translation (proteins/antibodies).
Production of therapeutic proteins necessitates comprehensive understanding of the target protein's function, structure, and the encoding gene's sequence.

Recombinant DNA technology surpasses traditional protein extraction from biological sources by addressing several challenges:
- Availability: Generates proteins that may be scarce in natural sources.
- Safety: Reduces risks of disease transmission from human and animal sources (e.g., HIV, hepatitis, Creutzfeldt-Jakob).
- Quantity: Allows for higher yields of proteins, making the process more cost-effective.
- Engineering: Facilitates modifications for improved clinical outcomes, such as altered pharmacokinetics and extended half-life through mutagenesis or addition of molecules (e.g., PEG).

Small molecule production begins with classical screening from various sourcing (microbes, plants, libraries).
Active compounds are identified through in vitro assays followed by in vivo tests to confirm efficacy.
Pre-clinical studies must be conducted, including pharmacological evaluation, pharmacokinetics (PK), pharmacodynamics (PD), and toxicological assessments.

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