ORAL BIOAVAILABILITY OF LOW-DOSE (20MG) HOME-MADE ETOPOSIDE CAPSULES

The oral bioavailability of etoposide 20mg capsules, which were manufa ctured in our hospital pharmacy, was studied in 14 patients with vario us types of solid tumours. The presence of the lubricant colloidal sil icium dioxide (Aerosil(R) 200) significantly decreased the oral bioava ilability of etoposide (p = 0.044). The median bioavailability for the capsules without the lubricant was 33.5% (range 20.8 to 69.0%; n = 12 ). After intravenous and oral administration, the median elimination h alf-lives were 3.8 (range 1.9 to 9.4 hours) and 8.7 hours (range 2.2 t o 22.5 hours) [p = 0.015], respectively, and the mean residence times were 4.9 (range 2.3 to 11.4 hours) and 12.6 hours (range 4.2 to 31.3 h ours) [p = 0.010], respectively. It is concluded that the bioavailabil ity of etoposide reported in this study (33.5%) is lower than the norm al value of about 70 to 80% for commercially available etoposide capsu les (Vepesid(R); low dose). This can be explained by the fact that in the '-home-made'' formulation etoposide has been processed as a solid and so dissolution has become a rate-limiting step in the absorption a nd disposition from the gastrointestinal tract, while in the Vepesid(R ) capsules etoposide has been solubilised in a co-solvent formulation and is readily available for absorption.