The Pharmacokinetic Driver Of Thrombocytopenia And Its Implications For Clinical Dose Schedule Optimization.

e20726 Background: Therapeutic intervention in oncology often results in thrombocytopenia. Clinical schedule modification may be used to mitigate thrombocytopenia in patients. Prior knowledge of the pharmacokinetic (PK) driver of toxicity provides useful insights for effectively managing thrombocytopenia. In this work, we propose that scheduling effects for toxicities resulting from myelosupression such as thrombocytopenia are a function of the biological system and thus independent of the compound. Using data from published clinical models, we have identified a PK correlate of thrombocytopenia toxicity. Methods: Clinical platelet time-profile resulting from different schedules was simulated for Abexinostat, Carboplatin and Linezolid using published PK/PD models. Platelet nadir, probability of grade-4 thrombocytopenia and probability of grade-4 thrombocytopenia u003e 7 days were correlated with AUC and Cmax. In a previous publication we had identified a novel PK parameter, the maximum moving average concentra...