Why consider them as a separate group?
Examples of macromolecular drugs include insulin, therapeutic enzymes, fusion proteins and monoclonal antibodies. This is not a uniform group: the characteristics described below primarily apply to therapeutic proteins, particularly large antibodies. Not every macromolecule is an antibody, and not every protein drug is long-acting.
The most important differences
| Aspect | Common characteristics of small-molecule drugs | Common characteristics of large therapeutic antibodies |
|---|---|---|
| Administration | Many drugs are effective when taken orally. | Usually parenteral, for example intravenous or subcutaneous; proteins are degraded in the gastrointestinal tract, and absorption of intact protein is limited. |
| Absorption after subcutaneous administration | Many small molecules enter blood capillaries directly. | Slow lymphatic uptake is often important for large antibodies; lymph ultimately drains into the bloodstream. |
| Distribution | Strongly influenced by lipophilicity, ionisation and transporters. | Also restricted by size, vascular permeability, convection and target binding; antibodies do not distribute freely into all cells. |
| Blood–brain barrier | Some lipophilic small molecules penetrate well. | Brain exposure to conventional antibodies is generally low when the barrier is intact, although not necessarily exactly zero. |
| Degradation | Many drugs are substrates of CYP enzymes and other drug-metabolising enzymes. | The protein component is mainly degraded into peptides and amino acids by proteolytic processes; the CYP system is not the main pathway. |
| Elimination | Various combinations of metabolism, renal excretion and biliary excretion. | Cellular uptake and catabolism, partly through target-mediated removal; glomerular filtration of intact, unchanged IgG is limited. |
| Time course | Highly variable; not every small molecule is short-acting. | Many intact IgGs persist for days to weeks; FcRn-mediated recycling also protects them from degradation. Fragments may behave differently. |
| Safety and clinical use | Risks depend on the drug and the patient. | Immunogenicity, allergy and non-allergic administration-related reactions can occur; supervision requirements depend on the product. |
These are common differences, not rules without exceptions. For example, the free plasma concentration of an antibody fragment may decline rapidly while its target-bound effect persists longer. Historical abciximab prescribing information
Four relationships worth understanding
1. Lymph and blood are not mutually exclusive pathways. The lymphatic route mainly explains the absorption of large proteins administered subcutaneously. Intravenous administration does not involve this absorption step. The bloodstream also plays an essential role in systemic distribution. Study of subcutaneous protein absorption
2. Degradation products can be reused. Amino acids released by proteolysis can enter the body’s amino acid pool. FcRn binds IgG in acidic endosomes and returns some of it to the cell surface, reducing lysosomal degradation. This is not the same as CYP-mediated metabolism. Experimental study of FcRn-mediated recycling
3. Transcytosis is not simple diffusion through a lipid membrane. Endocytosis → intracellular vesicular transport → exocytosis on the opposite side. In contrast, the paracellular route passes between cells. Tight junctions and restricted transport at the blood–brain barrier generally limit the entry of large antibodies; specially engineered receptor-mediated shuttle constructs can improve delivery. Antibody transport experiment, receptor-mediated brain delivery
4. Prolonged kinetics do not justify arbitrarily infrequent dosing. The interval is determined by a dosing regimen studied in relation to the specific drug’s exposure, target inhibition, efficacy and safety. Half-life and duration of action are not always identical. Target-mediated elimination and anti-drug antibodies can also modify pharmacokinetics. Regulatory assessment of erenumab
Clinical use and immunogenicity
They can cause allergic reactions, but not every administration-related reaction is an allergy. An anti-drug immune response can also cause loss of efficacy or altered elimination. Even a human antibody is not guaranteed to be free of immunogenicity. WHO: limitations of source-related name elements
Many infusions require supervised specialist care, but not every antibody requires inpatient hospital care. Rituximab requires a setting equipped to manage emergencies; several subcutaneous products can be administered at home after appropriate training and a medical decision. MabThera, Cimzia
The absence of CYP-mediated degradation does not mean the absence of drug interactions. Reducing inflammation can indirectly alter CYP activity and the concentrations of other drugs; the small-molecule component of a conjugated product may also undergo separate metabolism. Regulatory assessment of tocilizumab
The essential points of nomenclature at this stage
In historical names: -omab: mouse; -ximab: chimeric; -zumab: humanised; -umab: human. The preceding infix may indicate a broad target class: for example, li/lim for immunomodulation, ki/kin for interleukins, tu/tum for tumours, ci/c for cardiovascular targets and ne/n for neural targets. This is not a precise code for a target organ or indication. The arbitrary prefix does not convey pharmacological information.
The system has changed: source-related infixes were discontinued for newly assigned names in 2017; the new suffixes in the 2021/2022 system are -tug, -bart, -mig and -ment. Existing names were retained. The breakdown of the 25 names in the illustrative appendix is not intended to be memorised as a separate drug list. WHO’s new nomenclature scheme
Learning requirement for this chapter: understand the principles of nomenclature and the differences in pharmacokinetics, metabolism, transport and clinical use. Detailed targets, indications, doses and drug-specific adverse effects belong to the later study of individual drug groups.
Antibody names – an illustrative nomenclature appendix
Appendix to the brief general pharmacology overview in Chapter 52. Not an additional drug list to memorise. Precise indications and drug-specific details will be covered in the study of individual drug groups.
How should the names be read?
The historical scheme is: arbitrary prefix + broad target class + source infix + mab. Shortened infixes may refer to the same historical target class. The prefixes should not be assigned an independent pharmacological meaning.
- -o- + mab → -omab: mouse origin.
- -xi- + mab → -ximab: chimeric.
- -zu- + mab → -zumab: humanised.
- -u- + mab → -umab: human.
- A less common historical infix: -xizu-, the chimeric–humanised category.
Target-class infixes include li/lim/l (immunomodulation), ki/kin/k (interleukins), tu/tum (tumours), ci/c (cardiovascular), ne/n (neural), vi (viral) and so/s (bone). These are not fixed organ codes: for example, an antibody with a historical tumour-related name may later also have autoimmune indications. WHO historical tables
Examples
The target and disease columns only help illustrate the meaning of the name; they are not complete prescribing information. International INN spellings are used. Most examples are established antibodies introduced earlier; the requested migraine antibodies are more recent illustrative additions.
| INN and name breakdown | Meaning of the name elements | Actual molecular target | Example disease / area of use |
|---|---|---|---|
| basiliximab = basi-li-xi-mab | immunomodulatory, chimeric | CD25 / IL-2Rα | prevention of transplant rejection |
| infliximab = inf-li-xi-mab | immunomodulatory, chimeric | TNF-α | rheumatoid arthritis, Crohn’s disease |
| adalimumab = ada-lim-u-mab | immunomodulatory, human | TNF-α | rheumatoid arthritis, psoriasis |
| certolizumab pegol = certo-li-zu-mab + pegol | immunomodulatory, humanised; PEGylated Fab’ | TNF-α | rheumatoid arthritis, psoriasis |
| omalizumab = oma-li-zu-mab | immunomodulatory, humanised | IgE | allergic asthma, chronic spontaneous urticaria |
| mepolizumab = mepo-li-zu-mab | immunomodulatory, humanised | IL-5 | severe eosinophilic asthma |
| dupilumab = dupi-l-u-mab | immunomodulatory, human | IL-4Rα | atopic dermatitis, selected forms of asthma |
| tocilizumab = toci-li-zu-mab | immunomodulatory, humanised | IL-6 receptor | rheumatoid arthritis |
| ustekinumab = uste-kin-u-mab | interleukin-related, human | shared p40 subunit of IL-12/IL-23 | psoriasis, Crohn’s disease |
| secukinumab = secu-kin-u-mab | interleukin-related, human | IL-17A | psoriasis, psoriatic arthritis |
| rituximab = ri-tu-xi-mab | historical tumour target class, chimeric | CD20 | B-cell lymphoma, rheumatoid arthritis |
| alemtuzumab = alem-tu-zu-mab | historical tumour target class, humanised | CD52 | selected forms of multiple sclerosis |
| natalizumab = nata-li-zu-mab | immunomodulatory, humanised | α4 integrin | selected forms of multiple sclerosis |
| cetuximab = ce-tu-xi-mab | tumour target class, chimeric | EGFR | selected colorectal and head-and-neck cancers |
| trastuzumab = tras-tu-zu-mab | tumour target class, humanised | HER2 | HER2-positive breast cancer |
| bevacizumab = beva-ci-zu-mab | historical cardiovascular/angiogenesis-related target class, humanised | VEGF-A | antiangiogenic treatment of selected cancers |
| ipilimumab = ipi-lim-u-mab | immunomodulatory, human | CTLA-4 | immunotherapy of selected cancers |
| palivizumab = pali-vi-zu-mab | virus-related, humanised | RSV F protein | prevention of severe RSV disease in selected children |
| denosumab = deno-s-u-mab | bone-related, human | RANKL | osteoporosis; product-specific prevention of skeletal complications |
| evolocumab = evolo-c-u-mab | cardiovascular target class, human | PCSK9 | hypercholesterolaemia |
| alirocumab = aliro-c-u-mab | cardiovascular target class, human | PCSK9 | hypercholesterolaemia |
| erenumab = ere-n-u-mab | neural target class, human | CGRP receptor | migraine prevention |
| fremanezumab = frema-ne-zu-mab | neural target class, humanised | CGRP ligand | migraine prevention |
| abciximab = ab-ci-xi-mab | cardiovascular target class, chimeric Fab | platelet GPIIb/IIIa, αIIbβ3 | historical example of platelet aggregation inhibition in PCI |
| ibritumomab tiuxetan = ibri-tum-o-mab + tiuxetan | tumour target class, mouse antibody + chelator | CD20 | historical example of radioimmunotherapy in B-cell lymphoma |
Abciximab and ibritumomab tiuxetan are also historical examples: the table does not imply current availability in Hungary. Ibritumomab illustrates the meaning of -omab; it is not an additional detailed examination requirement. Muromonab-CD3 predates the standard WHO naming scheme, so the same segmentation should not be imposed on it.
Two misconceptions the table helps prevent
Target class is not the same as indication. Despite its historical -tu- infix, rituximab can also be used in autoimmune disease. The -ci- infix in bevacizumab does not mean that it is used exclusively for heart disease.
The source infix is not an allergy test. Humanised or human origin does not exclude an anti-drug immune response. The prolonged kinetics associated with intact IgG also cannot automatically be extended to every fragment with a -mab name.
The new system in brief
In 2017, source infixes were discontinued for newly assigned names. The scheme adopted in 2021 and published in 2022 uses new suffixes: -tug (monospecific intact immunoglobulin with unmodified constant regions), -bart (monospecific intact immunoglobulin with engineered constant regions), -mig (bispecific/multispecific) and -ment (immunoglobulin-derived fragments/constructs outside the preceding monospecific intact-antibody groups). Existing names were not changed. WHO’s new scheme
Sources for checking molecular targets
- Simulect, Remicade, Humira, Cimzia.
- Xolair, Nucala, Dupixent, RoActemra.
- Stelara, Cosentyx, MabThera, Lemtrada, Tysabri.
- Erbitux, Herceptin, Avastin, Yervoy, Synagis.
- Prolia, Repatha, Praluent, Aimovig, Ajovy.
- Abciximab: historical FDA prescribing information, Zevalin: historical regulatory assessment.