Vincristine pharmacokinetics after repetitive dosing in children

Gidding, Corrie; Boer, C.J. Meeuwsen-de; Koopmans, Pauline; Uges, Donald; Kamps, Willem A.; Graaf, Siebold S.N. de

doi:10.1007/s002800050968

Cited by 85 publications

(70 citation statements)

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“…Vincristine has been implicated as the cause of these motor impairments, because of its toxic effect on the peripheral nervous system. Vincristine-induced neurotoxicity is dose-related (Carbone et al, 1963) and causes a peripheral, symmetric mixed sensory-motor, and autonomic polyneuropathy which is more marked distally (Gidding et al, 1999). CNS toxicity from intravenous vincristine is rare, most likely due to poor penetration through the intact blood-brain barrier (Kellie et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Visuomotor control in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only

Buizer

Sonneville

Heuvel‐Eibrink

et al. 2005

J. Inter. Neuropsych. Soc.

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Treatment for childhood acute lymphoblastic leukemia (ALL), which includes CNS prophylaxis, is associated with central and peripheral neurotoxicity. The purpose of the present study was to analyze the effects of chemotherapy on various levels of visuomotor control in survivors of childhood ALL treated without cranial irradiation, and to identify risk factors for possible deficits. Visuomotor function was compared between children after treatment for ALL (n 5 34), children after treatment for Wilms tumor, which consists of non-CNS directed chemotherapy (n 5 38), and healthy controls (n 5 151). Three tasks were administered: a simple visual reaction time task and two tasks measuring visuomotor control with one requiring a higher level of cognitive control than the other. Visuomotor deficits were detected only in the ALL group, with poorer performance restricted to the condition requiring the highest level of control. Significant risk factors for poorer performance were female gender and a short time since end of treatment, and a trend was found for a young age at diagnosis. A high cumulative methotrexate dose was an adverse predictive factor in girls. The results indicate that chemotherapy-induced central neurotoxicity in childhood ALL treatment is associated with higher order visuomotor control deficits. Girls appear to be particularly vulnerable. (JINS, 2005, 11, 554-565.)

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Section: Introductionmentioning

confidence: 99%

Visuomotor control in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only

Buizer

Sonneville

Heuvel‐Eibrink

et al. 2005

J. Inter. Neuropsych. Soc.

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“…A two-compartment, firstorder pharmacokinetic model was fitted to the vincristine concentration data. Primary pharmacokinetic variables were estimated by maximum a posteriori parameter estimation with a Bayesian algorithm using the ADAPT II software package with priors from 32 previously studied patients (30,31,35,36). Factors of the variance model were fixed at a coefficient of 0.1 and an exponent of 2.0.…”

Section: Patientsmentioning

confidence: 99%

“…CL appeared to be faster in children than in adults (mean CL, 431 and 189 mL·min Ϫ1 ·m Ϫ2 , respectively) (29,30). Both intra-and interpatient variability turned out to be large in pediatric cancer patients (31).…”

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confidence: 99%

Pharmacokinetics of Vincristine Monotherapy in Childhood Acute Lymphoblastic Leukemia

Groninger¹,

Boer²,

Koopmans³

et al. 2002

Pediatr Res

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We studied vincristine pharmacokinetics in 70 children newly diagnosed with acute lymphoblastic leukemia, after a single dose of vincristine as monotherapy. Vincristine plasma concentrations were measured by HPLC analysis. A two-compartment, firstorder pharmacokinetic model was fitted to the data by maximum a posteriori parameter estimation. In this group of children pharmacokinetic factors were highly variable: median (25th and 75th percentiles) total body clearance, 228 (128 -360) Vincristine, one of the naturally occurring vinca alkaloids extracted from the leaves of the periwinkle plant Catharanthus roseus, continues to play a key role in the treatment of childhood ALL since its introduction in 1962 (1). Vincristine exerts an antimitotic effect (2-4) and induces apoptosis in various hematologic cell lines (5-8). Its antileukemic effect in vivo is determined by both variability in exposure of the leukemic cells and variability in sensitivity of the cells to the effect of vincristine. In vitro sensitivity of leukemic cells has been well studied (9), but the variability in exposure of leukemic cells in vivo has received less attention. Therefore, we studied vincristine pharmacokinetics in children newly diagnosed with ALL, after a single dose of vincristine.Vincristine-induced cell kill in a human lymphoblastic leukemia cell line was proportional to saturation of cellular binding sites (10), suggesting that the concentration of vincristine to which the cell is exposed is an important determinant of the antileukemic effect of vincristine. In vitro, vincristine accumulates in cells to concentrations as high as 500 times extracellular concentrations and is slowly released from the cells after restoration in drug-free medium (11, 12). Tissue distribution of vincristine was studied with 3 H-labeled vincristine in the rat and revealed accumulation in spleen, adrenal and thyroid glands, large and small intestines, heart, lung, kidney, liver, and marrow. Penetration in rat eye, fat, and brain tissue and in human cerebrospinal fluid appears to be very poor (13)(14)(15).The first pharmacokinetic studies on vincristine in man were performed when 3 H-labeled vincristine became available, 15 y after the introduction of vincristine in clinical practice. It was found that urinary excretion accounts for up to 12% of excreted radioactivity (16, 17). The biliary system appeared to be the principal route of excretion (13, 18 -20

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“…It is assumed that plants contain a big reservoir of drugs with anti-tumorigenic properties (Corson & Crews 2007), but so far only few plant-derived substances such as vincristine or paclitaxel have achieved clinical relevance as chemotherapeutic agents (Gidding et al 1999, Fitzpatrick & Wheeler 2003. However, during the recent years, a growing number of plant-derived drugs with anti-tumorigenic activities have been detected, one among them is curcumin (diferuloylmethane), a biphenolic natural product and the active component of turmeric (Curcuma longa), which gives Indian curry its yellow colour and distinctive taste ).…”

Section: Introductionmentioning

confidence: 99%

Curcumin acts as anti-tumorigenic and hormone-suppressive agent in murine and human pituitary tumour cells in vitro and in vivo

Schaaf¹,

Shan²,

Buchfelder³

et al. 2009

Endocrine-Related Cancer

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Curcumin (diferuloylmethane) is the active ingredient of the spice plant Curcuma longa and has been shown to act anti-tumorigenic in different types of tumours. Therefore, we have studied its effect in pituitary tumour cell lines and adenomas. Proliferation of lactosomatotroph GH3 and somatotroph MtT/S rat pituitary cells as well as of corticotroph AtT20 mouse pituitary cells was inhibited by curcumin in monolayer cell culture and in colony formation assay in soft agar. Fluorescence-activated cell sorting (FACS) analysis demonstrated curcumin-induced cell cycle arrest at G2/M. Analysis of cell cycle proteins by immunoblotting showed reduction in cyclin D 1 , cyclin-dependent kinase 4 and no change in p27 kip . FACS analysis with Annexin V-FITC/7-aminoactinomycin D staining demonstrated curcumin-induced early apoptosis after 3, 6, 12 and 24 h treatment and nearly no necrosis. Induction of DNA fragmentation, reduction of Bcl-2 and enhancement of cleaved caspase-3 further confirmed induction of apoptosis by curcumin. Growth of GH3 tumours in athymic nude mice was suppressed by curcumin in vivo. In endocrine pituitary tumour cell lines, GH, ACTH and prolactin production were inhibited by curcumin. Studies in 25 human pituitary adenoma cell cultures have confirmed the antitumorigenic and hormone-suppressive effects of curcumin. Altogether, the results described in this report suggest this natural compound as a good candidate for therapeutic use on pituitary tumours.

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Vincristine pharmacokinetics after repetitive dosing in children

Abstract: We conclude that both intrapatient and interpatient variability in vincristine pharmacokinetics is large in pediatric cancer patients and that variability, although significantly influenced by diagnosis, largely remains unpredictable.

Cited by 85 publications

References 0 publications

Visuomotor control in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only

Visuomotor control in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only

Pharmacokinetics of Vincristine Monotherapy in Childhood Acute Lymphoblastic Leukemia

Curcumin acts as anti-tumorigenic and hormone-suppressive agent in murine and human pituitary tumour cells in vitro and in vivo

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