How close are we to personalized mitotane dosing in the treatment of adrenocortical carcinoma? State of the art and future perspectives.

Autor:	Steenaard RV; Department of Internal Medicine, Máxima MC, Veldhoven, Eindhoven, The Netherlands.; Maastricht University, CAPHRI School for Public Health and Primary Care, Ageing and Long-Term Care, Maastricht, The Netherlands., Ettaieb MHT; Department of Internal Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands., Kerkhofs TMA; Department of Internal Medicine, Division of Medical Oncology, Maastricht University Medical Centre+, Maastricht, The Netherlands., Haak HR; Department of Internal Medicine, Máxima MC, Veldhoven, Eindhoven, The Netherlands.; Maastricht University, CAPHRI School for Public Health and Primary Care, Ageing and Long-Term Care, Maastricht, The Netherlands.; Department of Internal Medicine, Division of General Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Jazyk:	angličtina
Zdroj:	Expert opinion on drug metabolism & toxicology [Expert Opin Drug Metab Toxicol] 2021 Jun; Vol. 17 (6), pp. 677-683. Date of Electronic Publication: 2021 May 04.
DOI:	10.1080/17425255.2021.1921146
Abstrakt:	Introduction: Mitotane is the only drug registered specifically for adrenocortical carcinoma. Finding the optimal dose for a patient is difficult due to large differences in bioavailability, toxicity and effect. We therefore look to improve personalized dosing of mitotane. Areas Covered: We searched PubMed for studies related to mitotane dosing, pharmacokinetics, pharmacogenetics and combination therapy. Comparison of different dosing strategies have not resulted in an optimal advice. Several computerized pharmacokinetic models have been proposed to predict plasma levels. The current pharmacokinetic models do not explain the full variance in plasma levels. Pharmacogenetics have been proposed to find the unexplained variance. Studies on combination therapy have not yet led to a potential dose adjustment for mitotane. Expert Opinion: Computerized pharmacokinetics models are promising tools to predict plasma levels, further validation is needed. Pharmacogenetics are introduced in these models, but more research is required before clinical application. We believe that in the near future, personalized mitotane dosage will be aided by a validated web-based pharmacokinetic model with good predictive ability based primarily on clinical characteristics, adjustable for actual plasma levels and dosage.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu