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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Pharmacokinetics of 10-ethyl-10-deaza-aminopterin, edatrexate, given weekly for non-small-cell lung cancer.

We studied the pharmacokinetics of 10-ethyl-10-deaza-aminopterin (10-EdAM), edatrexate and its 7-hydroxy metabolite during a phase II trial of treatment in advanced non-small-cell lung cancer. A dose of 80 mg/m2 was given weekly, with dose reduction being undertaken for mucositis or haematological toxicity. A triphasic pattern of plasma elimination was seen, the mean half-lives being 0.10 +/- 0.07, 0.8 +/- 0.3 and 7 +/- 7 h, respectively. The mean plasma clearance was 25 +/- 14 l/h, with 18% +/- 11% of the dose appearing unchanged in the urine. The serum concentration at 1 h accurately predicted the area under the curve (AUC) with r2 = 0.976. There was considerable variation of the clearance both within and between patients but there was no evidence of a dependence on time or dose. The 1-h concentration of the drug was shown to be related to the incidence of toxicity requiring dose reduction. The change in WBC due to the initial dose was shown to be related to both the AUC of the drug and that of its 7-OH metabolite.[1]

References

  1. Pharmacokinetics of 10-ethyl-10-deaza-aminopterin, edatrexate, given weekly for non-small-cell lung cancer. Hartley, J.M., Nicholson, P.W., Allen, R., Lamond, P., Harland, S.J., Souhami, R.L. Cancer Chemother. Pharmacol. (1993) [Pubmed]
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