Cancers, Vol. 12, Pages 1789: Population Pharmacokinetics of Vincristine Related to Infusion Duration and Peripheral Neuropathy in Pediatric Oncology Patients
We described PK differences related to administration duration and the relation between PK and VCR-induced peripheral neuropathy (VIPN). PK was assessed in 1–5 occasions (1–8 samples in 24 h per occasion). Samples were analyzed using high-performance liquid chromatography/tandem mass spectrometry. Population PK of VCR and its relationship with administration duration was determined using a non-linear mixed effect. We estimated individual post-hoc parameters: area under the concentration time curve (AUC) and maximum concentration (Cmax) in the plasma and peripheral compartment. VIPN was assessed using Common Terminology Criteria for Adverse Events (CTCAE) and the pediatric-modified total neuropathy score (ped-mTNS). Overall, 70 PK assessments in 35 children were evaluated. The population estimated that the intercompartmental clearance (IC-Cl), volume of the peripheral compartment (V2), and Cmax were significantly higher in the push group. Furthermore, higher IC-Cl was significantly correlated with VIPN development. Administration of VCR by push led to increased IC-Cl, V2, and Cmax, but were similar to AUC, compared to 1 h infusions. Administration of VCR by 1 h infusions led to similar or higher exposure of VCR without increasing VIPN.
Source: Cancers - Category: Cancer & Oncology Authors: Mirjam Esther van de van de Velde John Carl. Panetta Abraham J. Wilhelm Marleen H. van den van den Berg Inge M. van der van der Sluis Cor van den van den Bos Floor C.H. Abbink Marry M. van den van den Heuvel-Eibrink Heidi Segers Christophe Chantrain Jutte Tags: Article Source Type: research
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