Lack of correlation between methotrexate concentrations in serum, saliva and sweat after 24 h methotrexate infusions.

Jensen, K.H.; Brandsborg, M.

doi:10.1111/j.1365-2125.1987.tb03208.x

Cited by 12 publications

(8 citation statements)

References 13 publications

(21 reference statements)

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“…Several investigators have reported an even lower ratio of 1 to 2.3% between measured salivary and serum concentrations of MTX in patients who received HD-MTX [5,8]. Although only 50 to 70% of MTX in serum is bound to protein and the remaining 30 to 5070, as free MTX, might be expected to contribute to the salivary MTX concentration, the low observed salivary MTX levels might be attributable to either a physiological barrier against MTX influx into saliva or its rapid removal from saliva [ 5 ] .…”

Section: Discuss I 0 Nmentioning

confidence: 98%

Oral mucositis and salivary methotrexate concentration in intermediate‐dose methotrexate therapy for children with acute lymphoblastic leukemia

Ishii

Yamada

Higuchi

et al. 1989

Med. Pediatr. Oncol.

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The relationship between salivary methotrexate (MTX) concentration and severity of oral mucositis after administration of MTX was investigated in six children with acute lymphoblastic leukemia. They received two administrations of MTX at 500 mg/m2 with one third given bolusly and the remainder by 24-hour continuous infusion. No significant difference among patients or administration session was observed in serum MTX concentration. Detectable concentrations of salivary MTX (greater than 0.01 microM) were observed during nine of the ten infusions. A concentration of 0.1 microM or more, apparently lasting at least 12 hours, was observed during one infusion and followed by severe mucositis. During two of the ten infusions for different patients, concentrations of 0.04 to 0.07 microM and 0.02 to 0.04 microM, apparently lasting at least 12 and 18 hours, respectively, were observed, followed by moderate mucositis. During the other seven infusions, either much shorter or no increase in salivary MTX concentration was observed, with only mild or no subsequent mucositis. Analysis by Kendall's rank method showed a statistical correlation between concentration at 6 hours of infusion and severity of oral mucositis. The findings suggest that the early secretion of MTX into saliva has a significant role in the development of oral mucositis in leukemic children.

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Section: Discuss I 0 Nmentioning

confidence: 98%

Oral mucositis and salivary methotrexate concentration in intermediate‐dose methotrexate therapy for children with acute lymphoblastic leukemia

Ishii

Yamada

Higuchi

et al. 1989

Med. Pediatr. Oncol.

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“…This was achieved by the use of human tumour cell lines covering the spectrum of MTX-sensitive tumours (Jolivet et al, 1983), by selection of a 24 h MTX exposure period and by using MTX and FA concentrations representative of the clinical context (Stoller et al, 1977;Straw et al, 1984;Parker et al, 1986;Milano et al, 1986;Schroder et al, 1987;Borsi & Moe, 1987;Schilsky et al, 1989). Among the clinically relevant conclusions which can be drawn from the present study, the optimum time interval between MTX and FA appears to be around 18-24 h; a marked reduction in MTX cytotoxicity occurs during shorter intervals.…”

Section: Discussionmentioning

confidence: 99%

Critical factors for the reversal of methotrexate cytotoxicity by folinic acid

Bernard

Etienne²,

Fischel³

et al. 1991

Br J Cancer

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Summary The cytotoxicity of methotrexate (MTX) on representative human tumour cell lines (two cell lines from head and neck carcinomas, two from breast carcinomas, two from osteosarcomas and one lymphoblastoid cell line) was evaluated to: (1) examine the optimal time interval between MTX and folinic acid (FA) administration; (2) (FBS) were from Gibco (Paisley, UK). Penicillin and streptomycin were from Merieux (Lyons, France). Transferrin was from Flow Laboratories (Irvin, UK). The MTT test was performed with 3-(4-5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and DMSO, both from Sigma. Cell culturesThe eight human tumour cell lines used are described in Table I. Cells were routinely cultured in a humidified incubator (Sanyo) at 37'C with an atmosphere containing 8% CO2 in air. The head and neck cancer cell lines and the osteosarcoma cell lines were grown in DMEM medium supplemented with 10% FBS, penicillin (50,000 IU I1), streptomycin (86 tLM), and 1-glutamine (2 mM). The breast cancer cell lines were grown in the same medium supplemented with insulin (0.1 jIM) and transferrin (0.64 liM). The lymphoblastoid cell line was grown in RPMI 1640 medium supplemented with 10% FBS, penicillin (50,000 IU 1'), streptomycin (86 fLM) and 1-glutamine (2 mM). In brief, cells were grown in 96-well microtitration plates in their respective culture medium; 24 h later, they were exposed to MTX for 24 h. The respective initial cellular densities (Table I) were determined by a preliminary study in order to obtain optimal logarithmic growth. The MTX concentrations used (Table I)

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“…A small amount of MTX is excreted into saliva and sweat. Schrøder et al [133] reported the variation of the MTX excretion into saliva and sweat after 24 h continuous MTX infusion (0.5–6 g/m 2 ) in 14 patients with various malignant diseases. In the study, there were two patients, whose renal MTX excretions were markedly delayed, and in one of them, the salivary MTX elimination was also retarded.…”

Section: Introduction For Methotrexatementioning

confidence: 99%

Involvement of Multiple Transporters-mediated Transports in Mizoribine and Methotrexate Pharmacokinetics

Murakami

Mori

2012

Pharmaceuticals

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Mizoribine is administered orally and excreted into urine without being metabolized. Many research groups have reported a linear relationship between the dose and peak serum concentration, between the dose and AUC, and between AUC and cumulative urinary excretion of mizoribine. In contrast, a significant interindividual variability, with a small intraindividual variability, in oral bioavailability of mizoribine is also reported. The interindividual variability is mostly considered to be due to the polymophisms of transporter genes. Methotrexate (MTX) is administered orally and/or by parenteral routes, depending on the dose. Metabolic enzymes and multiple transporters are involved in the pharmacokinetics of MTX. The oral bioavailability of MTX exhibits a marked interindividual variability and saturation with increase in the dose of MTX, with a small intraindividual variability, where the contribution of gene polymophisms of transporters and enzymes is suggested. Therapeutic drug monitoring of both mizoribine and MTX is expected to improve their clinical efficacy in the treatment of rheumatoid arthritis.

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Lack of correlation between methotrexate concentrations in serum, saliva and sweat after 24 h methotrexate infusions.

Cited by 12 publications

References 13 publications

Oral mucositis and salivary methotrexate concentration in intermediate‐dose methotrexate therapy for children with acute lymphoblastic leukemia

Oral mucositis and salivary methotrexate concentration in intermediate‐dose methotrexate therapy for children with acute lymphoblastic leukemia

Critical factors for the reversal of methotrexate cytotoxicity by folinic acid

Involvement of Multiple Transporters-mediated Transports in Mizoribine and Methotrexate Pharmacokinetics

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