Optimization of oral etoposide dosage in elderly patients with non-Hodgkin's lymphoma using the fraction of dose absorbed measured for each patient

This study was undertaken to investigate the pharmacokinetics of etoposide for optimizing its oral dosage in elderly patients with non-Hodgkin's lymph oma (NHL) using the fraction of dose absorbed calculated from the data gene rated from first oral and intravenous doses in the same patient. Twenty-thr ee NHL patients (ages 61-95 years) entered this study. Each received 50 mg/ m(2) of etoposide by 1-hour IV infusion, which was repeated every 24 hours for 5 days. The second cycle commenced on day 21, with etoposide being admi nistered by mouth at a dose as close to 50 mg/m(2) as possible. Serial bloo d samples were collected and analyzed for etoposide by HPLC. The fraction o f dose absorbed (F) was calculated as F = (AUC(or)/AUC(iv)) (D-iv/D-or), an d etoposide was then given orally for the following 20 days at a daily dose equivalent to D-or/F. After 1 week free of etoposide administration, a sec ond cycle of oral etoposide at the adjusted dose was given for 21 days. The mean +/- SD vaIuesfor t(1/2 beta), t(max), C-max, CLTor, and MRT observed following the first oral dose were 8.98 +/- 4.84 h, 1.39 +/- 0.96 h, 0.083 +/- 0.046 mg.L-1/mg.m(-2), 1.89 +/- 1.2 L.h(-1)/m(2), and 10.37 +/- 2.76 h, respectively and those observed following the first intravenous dose were 8.05 +/- 5.11 h, 1.57 +/- 0.17 h, 0.142 +/- 0.043 mg.L-1/mg.m(-2), 1.25 +/- 0.44 L.h(-1)/m(2), and 7.69 +/- 1.53 h, respectively. The mean +/- SD of F was 0.80 +/- 0.34. The data obtained indicate that optimization of etoposi de oral dosage using F yielded good clinical results while keeping the morb idity at a level that is similar to that of the IV administration. Journal of Clinical Pharmacology, 2000;40:153-160 (C)2000 the American College of C linical Pharmacology.