Plasma and salivary pharmacokinetics of 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer receiving 5-FU bolus plus continuous infusion with high-dose folinic acid

Joulia, Jean Michel; Pinguet, Frédèric; Ychou, Marc; Duffour, Jacqueline; Astre, C.; Bressolle, Françoise

doi:10.1016/s0959-8049(98)00318-9

Cited by 35 publications

(35 citation statements)

References 20 publications

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“…Plasma concentrations after continuous infusion range from 0.1 to 8.8 µM, depending on the dose (300-2300 mg m À2 day À1 ) (Grem, 2000). In the mouth, saliva levels during continuous infusion range from 0.08 to 0.8 µM (Joulia et al, 1999), hence significantly lower than what can be measured in plasma but still high enough to affect the most sensitive micro-organisms in the mouth. Furthermore, plasma concentrations can reach much higher concentrations in DPDdeficient patients due to the tenfold longer half-life time of 5-FU (Saif et al, 2009).…”

Section: Discussionmentioning

confidence: 80%

“…Notwithstanding the fact that after an intravenous bolus injection with 5-FU, plasma concentrations in cancer patients can reach some hundred micromolars, the plasma levels eventually drop to 15-30 µM after 30 min and to 0 µM after 2 h (Casale et al, 2004;Kosovec et al, 2008), owing to the short half-life time (6-22 min) of 5-FU (Bocci et al, 2000). In the case of continuous infusion with 5-FU, the plasma concentrations are much lower, ranging from 3 to 10 µM and kept for a longer time period (24 h) (Joulia et al, 1999;Takimoto et al, 1999). It is, therefore, of interest to investigate the putative antimicrobial effect of physiologically relevant 5-FU concentrations on commensal micro-organisms in the context of oral mucositis.…”

Section: Introductionmentioning

confidence: 99%

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5-Fluorouracil sensitivity varies among oral micro-organisms

Vanlancker

Vanhoecke

Smet

et al. 2016

Journal of Medical Microbiology

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5-Fluorouracil (5-FU), a commonly used chemotherapeutic agent, often causes oral mucositis, an inflammation and ulceration of the oral mucosa. Micro-organisms in the oral cavity are thought to play an important role in the aggravation and severity of mucositis, but the mechanisms behind this remain unclear. Although 5-FU has been shown to elicit antibacterial effects at high concentrations (>100 µM), its antibacterial effect at physiologically relevant concentrations in the oral cavity is unknown. This study reports the effect of different concentrations of 5-FU (range 0.1-50 µM) on the growth and viability of bacterial monocultures that are present in the oral cavity and the possible role in the activity of dihydropyrimidine dehydrogenase (DPD), an enzyme involved in 5-FU resistance. Our data showed a differential sensitivity among the tested oral species towards physiological concentrations of 5-FU. Klebsiella oxytoca, Streptococcus salivarius, Streptococcus mitis, Streptococcus oralis, Pseudomonas aeruginosa and Lactobacillus salivarius appeared to be highly resistant to all tested concentrations. In contrast, Lactobacillus oris, Lactobacillus plantarum, Streptococcus pyogenes, Fusobacterium nucleatum and Neisseria mucosa showed a significant reduction in growth and viability starting from very low concentrations (0.2-3.1 µM). We can also provide evidence that DPD is not involved in the 5-FU resistance of the selected species. The observed variability in response to physiological 5-FU concentrations may explain why certain microbiota lead to a community dysbiosis and/or an overgrowth of certain resistant micro-organisms in the oral cavity following cancer treatment.

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Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

5-Fluorouracil sensitivity varies among oral micro-organisms

Vanlancker

Vanhoecke

Smet

et al. 2016

Journal of Medical Microbiology

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“…Lastly, 5-FU influences salivary excretion by decreasing the salivary flow rate-not only due to simple passive diffusion but also by an active process-thus fostering the development of oral mucositis [13]. Nevertheless, further evidence is required to support these hypotheses.…”

Section: Sirsmentioning

confidence: 97%

Capecitabine-induced stomatitis: a likely pathogenetic mechanism of oral lichenoid mucositis

Mignogna

Fortuna

Falleti

et al. 2009

Eur J Clin Pharmacol

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“…Este fenômeno pode ser devido a alterações na função das glândulas salivares causadas pelo 5-FU, resultando na redução da taxa de fluxo salivar Hayashi et al, 1988a;Slavik et al, 1993;Meurman et al, 1994;Joulia et al, 1999).…”

Section: Chromatography -Hplc)unclassified

“…Outras toxicidades, com uma baixa incidência são: síndrome mão-pé, alopécia, náuseas, vômitos, dermatite, toxicidades cardíacas e diminuição da secreção da glândula salivar Slavik et al, 1993;Joulia et al, 1999). De acordo com os trabalhos citados, César et al,…”

Section: Chromatography -Hplc)unclassified

Determinação da presença de 5-FU na saliva de hamsters que receberam o quimioterápico pela técnica de Cromatografia Líquida de Alta Eficiência

Benites¹

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Aconteça o que for, conte comigo! Ao grande amigo Ezequias Costa Rodrigues Júnior, ou só ZECA, muito obrigado por tudo. Pelas conversas, risadas, os post-it, a pasta para organizar melhor os artigos, a confecção da aula, enfim, você abrilhantou a minha jornada e, mais do que ninguém me incentiva a continuar buscando as realizações profissionais. Que a distância não seja empecilho para essa amizade! Ao meu amigo Tiago Machado, que é uma pessoa muito querida. Agradeço toda atenção que teve comigo no meu exame de qualificação. Divido com você também essa conquista.Ao amigo Bruno Lopes, ou apenas amiche, agradeço pela parceria e por todas as risadas que tivemos durante esse tempo na pós-graduação. É um cara do bem, de bom coração e sempre que precisei você estava pronto para me ajudar.

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Plasma and salivary pharmacokinetics of 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer receiving 5-FU bolus plus continuous infusion with high-dose folinic acid

Cited by 35 publications

References 20 publications

5-Fluorouracil sensitivity varies among oral micro-organisms

5-Fluorouracil sensitivity varies among oral micro-organisms

Capecitabine-induced stomatitis: a likely pathogenetic mechanism of oral lichenoid mucositis

Determinação da presença de 5-FU na saliva de hamsters que receberam o quimioterápico pela técnica de Cromatografia Líquida de Alta Eficiência

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