TY - JOUR
T1 - Population pharmacokinetics of vincristine related to infusion duration and peripheral neuropathy in pediatric oncology patients
AU - van de Velde, Mirjam Esther
AU - Panetta, John Carl
AU - Wilhelm, Abraham J.
AU - van den Berg, Marleen H.
AU - van der Sluis, Inge M.
AU - van den Bos, Cor
AU - Abbink, Floor C.H.
AU - van den Heuvel-Eibrink, Marry M.
AU - Segers, Heidi
AU - Chantrain, Christophe
AU - Bosch, Jutte van der Werff Ten
AU - Willems, Leen
AU - Evans, William E.
AU - Kaspers, Gertjan L.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Vincristine (VCR) is frequently used in pediatric oncology and can be administered intravenously through push injections or 1 h infusions. The effects of administration duration on population pharmacokinetics (PK) are unknown. 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.
AB - Vincristine (VCR) is frequently used in pediatric oncology and can be administered intravenously through push injections or 1 h infusions. The effects of administration duration on population pharmacokinetics (PK) are unknown. 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.
UR - http://www.scopus.com/inward/record.url?scp=85088880939&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers12071789
DO - https://doi.org/10.3390/cancers12071789
M3 - Article
C2 - 32635465
SN - 2072-6694
VL - 12
SP - 1
EP - 15
JO - Cancers
JF - Cancers
IS - 7
M1 - 1789
ER -