No evidence of gemcitabine accumulation during weekly administration.
Some anticancer agents tend to accumulate during repeated administration. We determined whether gemcitabine or its metabolites would accumulate during repeated administration. Gemcitabine was administered over two courses with each course consisting of a 30-min infusion at 1000 mg/m(2) weekly for 3 weeks followed by 1 week of rest. In 14 patients we evaluated eventual accumulation by comparing the concentrations in blood samples taken before, and at 30 and 60 min after the start of infusion on days 1, 8 and 15, in both cycles. At the end of the infusion gemcitabine concentrations at day 1 of both courses varied between 18 and 77 microM and at day 15 between 13 and 90 microM. The mean ratios day 8/day 1 and day 15/day 1 varied from 0.94 to 1.18. For the inactive metabolite 2',2'-difluoro-2'-deoxyuridine (dFdU) these values varied between 54 and 152 microM and 55 and 157, respectively, and the ratios from 0.96 to 1.08. The concentration of the active metabolite of gemcitabine, gemcitabine triphosphate (dFdCTP) in peripheral white blood cells, ranged between 37 and 283 pmol/10(6) cells at the end of infusion on day 1 and 35 and 115 pmol/10(6) cells on day 15. Potential accumulation was evaluated using a mixed effects model and no evidence was observed of accumulation for either gemcitabine or its metabolites. Gemcitabine can be administered safely without the risk that the drug will accumulate.[1]References
- No evidence of gemcitabine accumulation during weekly administration. de Lange, S.M., van der Born, K., Kroep, J.R., Jensen, H.A., Pfeiffer, P., Cleverly, A., van Groeningen, C.J., Peters, G.J. Eur. J. Clin. Pharmacol. (2005) [Pubmed]
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