Effects of high-dose cytarabine

Area of Science:

• Pharmacology
• Oncology
• Clinical Chemistry

Background:

• Cytarabine (ara-C) is a chemotherapy agent used in treating various cancers.
• Understanding its pharmacokinetic profile is crucial for optimizing treatment and managing side effects.

Purpose of the Study:

• To quantify cytarabine (ara-C) concentrations in plasma, urine, cerebrospinal fluid, and tears.
• To evaluate the pharmacokinetic profile of high-dose cytarabine (ara-C) therapy.
• To investigate the potential link between tear ara-C levels and conjunctivitis.

Main Methods:

• Measured ara-C concentrations using high-pressure liquid chromatography and radioimmunoassay in 15 patients.
• Administered high-dose IV ara-C (3 gm/m2) over 6 days.
• Analyzed plasma, urine, cerebrospinal fluid, and tear samples.

Main Results:

• Peak plasma ara-C concentrations were 50 times higher than with conventional doses.
• Cerebrospinal fluid ara-C concentrations were 10 times higher than with conventional intravenous dosing.
• Tear concentrations of ara-C were detected in patients with conjunctivitis, suggesting a possible causal link.

Conclusions:

• High-dose cytarabine (ara-C) administration leads to significantly elevated drug levels in plasma and cerebrospinal fluid.
• The elimination half-life and kinetics of ara-C remain largely unchanged despite high-dose or repeated dosing.
• The presence of ara-C in tears may contribute to the development of conjunctivitis in patients undergoing high-dose therapy.