Pharmacokinetics and pharmacodynamics of weekly epoetin beta in lung cancer patients.

BACKGROUND To assess the pharmacokinetic profile and time-course of trough concentrations and hemoglobin levels associated with subcutaneous weekly administration of epoetin beta in lung cancer patients with chemotherapy-induced anemia. METHODS Epoetin beta was subcutaneously administered to 15 anemic lung cancer patients once weekly for 8 weeks at doses of 9000, 18,000 and 36,000 IU. Pharmacokinetic parameters (C(max), AUC(inf) and T(1/2)) were determined after the first single dose administration on a model-independent basis, and the relationship between the dose and these parameters was examined for linearity. RESULTS Weekly administration of epoetin beta at 9000, 18,000 and 36,000 IU produced C(max) values of 308 +/- 117 (mean +/- standard deviation), 678 +/- 86.7 and 1316 +/- 766 mIU/ml, and AUC(inf) values of 15,300 +/- 9524, 54,574 +/- 16,265 and 88,501 +/- 55,687 hr mIU/ml, respectively, showing dose-proportional increases. Trough concentrations tended to increase in the presence of severe bone marrow suppression induced by chemotherapy or other factors. Extremely high values were seen in three patients, but there was no apparent trend toward an increase with repeated doses. After 8 weeks' administration at 9000, 18,000 and 36,000 IU, hemoglobin levels were changed by -0.37 +/- 1.26, 2.15 +/- 1.36 and 2.82 +/- 2.17 g/dl, respectively. CONCLUSIONS Epoetin beta exhibited linear pharmacokinetics when administered to anemic cancer patients at weekly doses of 9000-36,000 IU and did not cause drug accumulation. Hemoglobin levels increased with weekly doses of 18,000 or 36,000 IU.