A highly sensitive bioanalytical method for the quantification of vinblastine, vincristine, vinorelbine and 4-O-deacetylvinorelbine in human plasma using LC-MS/MS

Heijden, Lisa T van der; Gebretensae, A.; Thijssen, Bram; Andel, L. van; Nijstad, A. Laura; Wang, Y.; Rosing, Hilde; Huitema, Alwin D. R.; Beijnen, Jos H.

doi:10.1016/j.jpba.2022.114772

Cited by 7 publications

(5 citation statements)

References 16 publications

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“…Two milliliters of venous samples were collected at 60 (±15), 90 (±5), and 240 (±15) minutes after the end of vincristine intravenous (IV) push administration 18 . The samples were shipped temperature‐controlled to the Netherlands, where the vincristine concentration was determined using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) 19 . Vincristine exposure was assessed using a pharmacometric nomogram in which the ratio between the individual observed concentration and the median concentration of European patients was determined 18 .…”

Section: Methodsmentioning

confidence: 99%

“…19 Vincristine exposure was assessed using a pharmacometric nomogram in which the ratio between the individual observed concentration and the median concentration of European patients was determined. 18 of 2 and 5 and higher indicating VIPN. 21 VIPN assessments were performed at baseline, before, and 1 week after a dose, and at least monthly.…”

Section: Study Interventionmentioning

confidence: 97%

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Vincristine exposure in Kenyan children with cancer: CHAPATI feasibility study

Uittenboogaard,

van de Velde,

van de Heijden

et al. 2024

Pediatric Blood & Cancer

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The low incidence of vincristine‐induced peripheral neuropathy (VIPN) in Kenyan children may result from low vincristine exposure. We studied vincristine exposure in Kenyan children and dose‐escalated in case of low vincristine exposure (NCT05844670). Average vincristine exposure was high. Individual vincristine exposure was assessed with a previously developed nomogram. A 20% dose increase was recommended for participants with low exposure and no VIPN, hyperbilirubinemia, or malnutrition. None of the 15 participants developed VIPN. Low vincristine exposure was seen in one participant: a dose increase was implemented without side effects. In conclusion, the participants did not develop VIPN despite having high vincristine exposure.

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Section: Methodsmentioning

confidence: 99%

Section: Study Interventionmentioning

confidence: 97%

Vincristine exposure in Kenyan children with cancer: CHAPATI feasibility study

Uittenboogaard,

van de Velde,

van de Heijden

et al. 2024

Pediatric Blood & Cancer

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“…Genotypes for the CYP3A4 and CYP3A5 genes were not available at the time of execution of the current study. Samples were analyzed using a validated liquid chromatography tandem mass spectrometry (LC–MS/MS) method with a reported lower limit of quantification of 0.1 ng/mL [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

Model-Informed Precision Dosing to Reduce Vincristine-Induced Peripheral Neuropathy in Pediatric Patients: A Pharmacokinetic and Pharmacodynamic Modeling and Simulation Analysis

Centanni,

van de Velde,

Uittenboogaard

et al. 2023

Clin Pharmacokinet

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Background Vincristine-induced peripheral neuropathy (VIPN) is a common adverse effect of vincristine, a drug often used in pediatric oncology. Previous studies demonstrated large inter- and intrapatient variability in vincristine pharmacokinetics (PK). Model-informed precision dosing (MIPD) can be applied to calculate patient exposure and individualize dosing using therapeutic drug monitoring (TDM) measurements. This study set out to investigate the PK/pharmacodynamic (PKPD) relationship of VIPN and determine the utility of MIPD to support clinical decisions regarding dose selection and individualization. Methods Data from 35 pediatric patients were utilized to quantify the relationship between vincristine dose, exposure and the development of VIPN. Measurements of vincristine exposure and VIPN (Common Terminology Criteria for Adverse Events [CTCAE]) were available at baseline and for each subsequent dosing occasions (1–5). A PK and PKPD analysis was performed to assess the inter- and intraindividual variability in vincristine exposure and VIPN over time. In silico trials were performed to portray the utility of vincristine MIPD in pediatric subpopulations with a certain age, weight and cytochrome P450 (CYP) 3A5 genotype distribution. Results A two-compartmental model with linear PK provided a good description of the vincristine exposure data. Clearance and distribution parameters were related to bodyweight through allometric scaling. A proportional odds model with Markovian elements described the incidence of Grades 0, 1 and ≥ 2 VIPN overdosing occasions. Vincristine area under the curve (AUC) was the most significant exposure metric related to the development of VIPN, where an AUC of 50 ng⋅h/mL was estimated to be related to an average VIPN probability of 40% over five dosing occasions. The incidence of Grade ≥ 2 VIPN reduced from 62.1 to 53.9% for MIPD-based dosing compared with body surface area (BSA)-based dosing in patients. Dose decreases occurred in 81.4% of patients with MIPD (vs. 86.4% for standard dosing) and dose increments were performed in 33.4% of patients (no dose increments allowed for standard dosing). Conclusions The PK and PKPD analysis supports the use of MIPD to guide clinical dose decisions and reduce the incidence of VIPN. The current work can be used to support decisions with respect to dose selection and dose individualization in children receiving vincristine. Supplementary Information The online version contains supplementary material available at 10.1007/s40262-023-01336-1.

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“…12,13 Liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) has served as a reference method with high specificity and great accuracy in clinical laboratories over the last 10–15 years. 14 Recently, different LC-ESI-MS/MS methods for vincristine quantification have been reported, but almost all of them have a large plasma sample consumption 15,16 and complex sample clean-up methods, such as liquid–liquid extraction 17 and solid phase extraction, 18 or a longer analysis time for each sample 15 (Table 1). Hence, an appropriate method for quantifying vincristine in plasma for TDM is critical, especially in the pediatric population, which requires higher sensitivity in micro-volumes of plasma and achieves a lower limit of quantification (LLOQ).…”

Section: Introductionmentioning

confidence: 99%