Seek and destroy: improving PK/PD profiles of anticancer agents with nanoparticles.

Seek and destroy: improving PK/PD profiles of anticancer agents with nanoparticles. Expert Rev Clin Pharmacol. 2018 May 16;: Authors: Rodallec A, Fanciullino R, Lacarelle B, Ciccolini J Abstract BACKGROUND: The Pharmacokinetics/pharmacodynamics (PK/PD) relationships with cytotoxics are usually based on a steepening concentration-effect relationship; the greater the drug amount, the greater the effect. The Maximum Tolerated Dose paradigm, finding the balance between efficacy while keeping toxicities at their manageable level, has been the rule of thumb over the last 50-years. Developing nanodrugs is an appealing strategy to help broaden this therapeutic window. The fact that efficacy and toxicity with cytotoxics are intricately linked is primarily due to the complete lack of specificity towards the tumor tissue during their distribution phase. Because nanoparticles are expected to better target tumor tissue while sparing healthy cells, accumulating large amounts of cytotoxics in tumors could be achieved in a safer way. Areas covered: This review aims at presenting how nanodrugs present unique features leading to reconsidering PK/PD relationships of anticancer agents. Expert commentary: The constant interplay between carrier PK plus specific interactions with cancer cells, payload release, payload PK, target expression and engagement, makes picturing the exact PK/PD relationships of nanodrugs particularly challenging. However those imp...
Source: Expert Review of Clinical Pharmacology - Category: Drugs & Pharmacology Tags: Expert Rev Clin Pharmacol Source Type: research