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Evidence for CSF accumulation of 5-methyltetrahydrofolate during repeated courses of methotrexate plus folinic acid rescue.

Abstract：

:In the first part of this study the availability of folinic acid (FA) and its main active circulating metabolite, 5-methyltetrahydrofolate (5-MTHF), were studied in plasma and cerebrospinal fluid (CSF) from normal subjects after i.v. administration of 100 and 250 mg of FA. 5-MTHF rapidly appeared in plasma, the maximum value being reached at the first observation time point (1 h). FA was eliminated in plasma more slowly than 5-MTHF. Between the two doses, there was no evidence of modification in pharmacokinetic parameters (terminal half-life, clearance) for either FA or 5-MTHF in plasma and CSF; 5-MTHF was the only product detectable in CSF. Considering FA plus 5-MTHF together, the AUC (area under the curve) ratios between CSF and plasma were close to 1%. 5-MTHF was cleared very slowly from CSF (t 1/2 = 85 h). This finding suggested possible accumulation of 5-MTHF in CSF during repeated administration of FA combined with medium or high dose MTX. In the second part of the study, dealing with a group of eight children treated by such protocols, an increase in CSF 5-MTHF was detected from cycle to cycle in five (r = 0.91, P less than 0.01) with a maximum at 5 x 10(-8) M. This progressive accumulation of 5-MTHF in CSF may have a negative effect on the local action of MTX and should be taken into account for therapeutic strategies designed for the management of meningeal leukaemia.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Thyss A,Milano G,Etienne MC,Paquis P,Roche JL,Grelier P,Schneider M

doi

10.1038/bjc.1989.127

subject

Has Abstract

pub_date

1989-04-01 00:00:00

pages

627-30

issue

4

eissn

0007-0920

issn

1532-1827

journal_volume

59

pub_type

杂志文章

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