Introduction
Biologicals -in this context mostly drugs that are recombinant therapeutic proteins, monoclonal antibodies (mAb), fusion proteins and conjugates- have entered many therapeutic areas in the last couple of decades.
The pharmacokinetic characteristics of such drugs differ in several aspects from the traditional small molecule drugs. The route of administration is frequently intravenous (iv) only, occasionally formulations for subcutaneous (sc) administration are available and may introduce a source of variation in bioavailability. Still, the most important factor giving rise to variability within and between patients, is the elimination of biological drugs. The question is whether this leads to variations of a proportion suggesting that individualization of dosing is warranted. Currently, for most of the established therapies with biologicals, the dosage regimens are typically one recommended dose for all adults -or in some cases dose adjusted to bodyweight or body surface area.
In organ transplantation there are only a limited number of biologicals with immunosuppression after transplantation as the labelled indication. A few more may have labels relevant for treatment of conditions related to transplantation or the underlying disease. A number of biological drugs, however, are used off label on various indications in organ transplant recipients. Hopefully, in many cases it will serve the patient well, but unless this transforms into formal clinical studies of the new indication, it is difficult to aggregate experience with dosing versus response and toxicity and to optimize the treatment further by implementing therapeutic drug monitoring (TDM). Following a period of very few drugs reaching approval for the use in transplant recipients, there is currently a resurgence and a number of biologicals are in clinical testing, mostly for desensitization and treatment of antibody mediated rejections, but also for some other specific indications. Examples of such drugs are listed alongside drugs with approved indications in Table 1.