IS THERE A RELATIONSHIP BETWEEN CYTARABINE PHARMACOKINETICS AND KERATITIS - A CASE-REPORT

While on therapy for acute myeloid leukemia, a 15-year-old girl develo ped extensive punctate keratitis of both eyes following high-dose cyta rabine therapy (HD-Ara-C). Pharmacokinetic monitoring showed an increa se of the Ara-C plasma levels up to twice the steady-state level withi n 10 minutes after discontinuation of the Ara-C infusion. Calculations of Ara-C plasma half-life, plasma clearance and volume of distributio n were within the expected range. Owing to the short half-life of Ara- C in blood due to rapid deamination, varying infusion velocities will result in markedly varying plasma levels. Higher peak plasma levels le ad to proportionally higher diffusion into compartments like tears, aq ueous humor and cerebrospinal fluid. In compartments which lack notewo rthy deaminase activity, dose intensity will be much more enhanced tha n in plasma. Peak plasma levels, therefore, may be associated with mul tifold local toxicity without concurrent increase of hematological tox icity. Especially when the drug is given in small volumes of infusion, these considerations should be taken into account. Precise control of infusion parameters and application of artificial tears for dilution of the Ara-C concentration on the corneal surface should be part of ke ratitis prophylaxis.