Summary
The oral bioavailability of etoposide 20mg capsules, which were manufactured in our hospital pharmacy, was studied in 14 patients with various types of solid tumours. The presence of the lubricant colloidal silicium dioxide (Aerosil® 200) significantly decreased the oral bioavailability 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 half-lives were 3.8 (range 1.9 to 9.4 hours) and 8.7 hours (range 2.2 to 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 hours) [p = 0.010], respectively. It is concluded that the bioavailability of etoposide reported in this study (33.5%) is lower than the normal value of about 70 to 80% for commercially available etoposide capsules (Vepesid®; 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 and disposition from the gastrointestinal tract, while in the Vepesid® capsules etoposide has been solubilised in a co-solvent formulation and is readily available for absorption.
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References
Slevin ML. Low-dose oral etoposide: a new role for an old drug [editorial]? J Clin Oncol 1990; 8: 1607–9
Slevin ML, Clark PI, Joel SP, et al. A randomized trial to evaluate the effect of schedule on the activity of etoposide in small cell lung cancer. J Clin Oncol 1989; 7: 1333–40
Clark PI, Slevin ML. The clinical pharmacology of etoposide and teniposide. Clin Pharmacokinet 1987; 12: 223–52
Thompson DS, Hainsworth JD, Hande KR, et al. Prolonged administration of low-dose, infusional etoposide in patients with etoposide-sensitive neoplasms: a phase I/II study. J Clin Oncol 1993; 11: 1322–8
Clark PI, Joel SP, Slevin ML. Apharmacokinetic hypothesis for the clinical efficacy of etoposide in small cell lung cancer. Proc Am Assoc Clin Oncol 1989; 8: 66
Slevin ML, Joel SP. Prolonged oral etoposide in small cell lung cancer [editorial]. Ann Oncol 1993; 4: 529–32
Herben VMM, Ten Bokkel Huinink WW, Rodenhuis S, et al. Phase I and pharmacokinetic study of topotecan in combination with oral etoposide. Eur J Cancer 1995; 31ASuppl. 5: S196
Herben VMM, Ten Bokkel Huinink WW, Rodenhuis S, et al. Phase I and pharmacokinetic study of topotecan in combination with oral etoposide. Eur J Cancer 1996; 7 Suppl. 1: 133
Kozelsky TK, Bonner JA. Sequence-dependent interaction of etoposide and topotecan. Proc Am Assoc Cancer Res 1995; 36: 293
Danks MK. Translocation of topoisomerase I from nuclei to cytoplasm of anaplastic astrocytoma cells by topotecan or VP-16. Proc Am Assoc Cancer Res 1995; 36: 450
Hainsworth JD, Johnson DH, Frazier SR, et al. Chronic daily administration of oral etoposide — a phase I study. J Clin Oncol 1989; 7: 396–401
Cavalli F, Zucchetti M, Gentili D, et al. Phase I and clinical pharmacological evaluation of daily oral etoposide (VP16). Proc ASCO 1992; 11: 109
Marzola M, Zucchetti M, Colombo N, et al. Low-dose oral etoposide in epithelial cancer of the ovary. Ann Oncol 1993; 4: 517–9
Van Warmerdam LJC, Verweij J, Schellens JHM, et al. Pharmacokinetics and pharmacodynamics of topotecan administered in a daily times five regimen every three weeks. Cancer Chemother Pharmacol 1995; 35: 237–45
Anonymous. Uniformity tests: dissolution test for solid oral dosage forms. European Pharmacopeia. 2nd ed. 225–225b; 225d-225g, Sdu Uitgeverij, ’s-Gravenhage, The Netherlands, 1983
Gibaldi M, Perrier D. Pharmacokinetics (revised and expanded). 2nd ed. New York: Marcel Dekker Inc., 1982: 409–17
Sinkule JA, Evans WE. High-performance liquid Chromatographic analysis of the semisynthetic epipodophyllotoxins teniposide and etoposide using electrochemical detection. J Pharm Sci 1984; 73: 164–86
Jonkman-de Vries JD, Rosing H, Van Tellingen O, et al. Pharmacokinetics of etoposide after oral and intravenous administration in patients with gastric carcinoma. Clin Drug Invest 1995; 10: 86–95
Hakata T, Ijima M, Kimura S, et al. Effects of bases and additives on release of carbon dioxide from effervescent suppositories. Chem Pharm Bull 1993; 41: 351–6
Dal Zotto M, Realdon N, Ragazzi E, et al. Effects of two different kinds of silicium dioxide on release of drugs from suppositories: benzydamine hydrochloride. Farmaco 1991; 46: 699–711
Bueno L, Fioramonti J. Action of opiates on gastrointestinal function. Baillieres Clin Gastroenterol 1988; 2: 123–9
Wood M. Pharmacokinetic drug interactions in anaesthetic practice. Clin Pharmacokinet 1991; 21: 285–307
Rowland M, Tozer T. Clinical pharmacokinetics, concepts and applications. 2nd ed. Philadelphia: Lea & Febiger, 1989: 113–30
Gibaldi M, Perrier D. Pharmacokinetics (revised and expanded). 2nd ed. New York: Marcel Dekker Inc., 1982: 34–5
Hande KR, Krozely MG, Greco FA, et al. Bioavailability of low-dose oral etoposide. J Clin Oncol 1993; 11: 374–7
Bernards JA, Bouman LN. Fysiologie van de mens, vijfde, herziene druk. Utrecht/Antwerpen: Bohn, Scheltema & Holkema, 1988: 388–93
Beijnen JH, Holthuis JJM, Kerkdijk HG, et al. Degradation kinetics of etoposide in aqueous solution. Int J Pharm 1988; 41: 169–78
Shah JC, Chen JR, Chow D. Preformulation study of etoposide: identification of physicochemical characteristics responsible for the low and erratic oral bioavailability of etoposide. Pharm Res 1989; 6: 408–12
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Jonkman-de Vries, J.D., Herben, V.M.M., van Tellingen, O. et al. Oral Bioavailability of Low Dose (20mg) ‘Home-Made’ Etoposide Capsules. Clin. Drug Invest. 12, 298–307 (1996). https://doi.org/10.2165/00044011-199612060-00003
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DOI: https://doi.org/10.2165/00044011-199612060-00003