L: Antineoplastic and immunomodulating agents
Group L holds the drugs used against cancer and the drugs that act on the immune system, either stimulating it or suppressing it.
| Description | In plain terms | Example drug | |
|---|---|---|---|
| L01 | Antineoplastic agents | drugs that kill or block tumor cells | Pembrolizumab (L01FF02) / trastuzumab (L01FD01) |
| L02 | Endocrine therapy | hormone-blocking therapy, mainly breast and prostate cancer | Tamoxifen (L02BA01) / anastrozole (L02BG03) |
| L03 | Immunostimulants | Filgrastim (L03AA02) / pegfilgrastim (L03AA13) | |
| L04 | Immunosuppressants | Tacrolimus (L04AD02) / adalimumab (L04AB04) |
Monoclonal antibodies
Monoclonal antibodies are found both in L01, for example the immune checkpoint inhibitors, and in L04A, for example the TNF-α and interleukin inhibitors.
Some drugs bind their target with such high affinity, and to such an extent, that the binding changes their pharmacokinetics. This is called target-mediated drug disposition (TMDD), and it is seen mostly with biologics such as monoclonal antibodies. Binding to the target and turnover of the drug-target complex then add to the elimination, and because the number of targets is finite, this elimination saturates and the pharmacokinetics become nonlinear. The full TMDD model has many parameters, so simpler approximations, such as the quasi-steady-state and Michaelis-Menten forms, were developed to make fitting it to data feasible [1].
For the antibodies approved in rheumatoid arthritis, the volume of distribution is low (3 to 4 L) and the elimination half-life is usually 2 to 3 weeks. Their clearance has a linear, non-specific part and a target-mediated part that is often nonlinear. The patient’s immune system can also form anti-drug antibodies, which speed up the elimination of the antibody [2].