[CYP3A inhibitors as a pharmacokinetic enhancer: pros and cons of drug interactions]. / CYP3A-remmers als farmacokinetische hulpstof.

Certain drugs inherently have unfavourable pharmacokinetic properties; for example, they are poorly absorbed or broken down too quickly in the liver. In some cases, the addition of a pharmacokinetic excipient, thus deliberately causing an interaction, may offer a solution. To date, this concept has been most widely applied in HIV treatment where addition of the CYP3A inhibitors ritonavir and cobicistat greatly increases plasma levels of other HIV medications. For the same reason, ritonavir has been added to the new oral antiviral drug against the SARS CoV-2 virus, nirmatrelvir. In addition to a better and/or longer effect, theoretically lower doses can also be used, resulting in cost savings. Deliberately inducing a pharmacokinetic interaction is not without risk: after all, interactions with other CYP3A substrates can also occur. Nevertheless, we believe that with good interaction management, CYP3A inhibitors can be used safely with benefits for patients and society.

[Hormone therapy in prostate cancer; a pharmacotherapeutic challenge]. / Hormonale therapie bij prostaatkanker; een farmacotherapeutische uitdaging.

Prostate cancer is the most common form of cancer in men in the Western world. One-third of the patients with localised prostate cancer will develop recurrent disease, localised disease spread or distant metastases. The presence of distant metastases is an indication for primary palliative hormone therapy. Intervention in the testosterone metabolism using hormone therapy is frequently accompanied by side effects and has a negative influence on the quality of life. Almost all prostate cancer patients show disease progression while on primary hormone therapy, despite having testosterone concentrations at castration level; they are then said to have castration-resistant prostate cancer (CRPC). The CYP17 inhibitor abiraterone and the non-steroidal anti-androgen enzalutamide are second-generation hormone therapies for metastatic CRPC both before and after treatment with standard docetaxel-based chemotherapy. Abiraterone and enzalutamide can lead to many interactions with other drugs or food. This can lead to higher or lower levels of both the hormone therapy and comedications.