Summary
Pharmacokinetic parameters established in 15 patients receiving parenterally administered etoposide (80–120 mg·m-2) are reported. The etoposide assay by means of mass spectrometry after sample separation by thin-layer chromatography or high-pressure liquid chromatography used in this study has been described else-where [4]. Peak plasma levels (9.5–63.3 μg·ml-1), the area under the curve (AUC) (2707–10192 μg·ml-1·min-1), the mean transit time MTT (2.7–10.6 h), etoposide half-lives t1/2α (0.10–0.52 h) and t1/2β (2.18–8.17 h), the volume of distribution at steady state (Vdss) (2.5–15.1·l/m-2) and the systemic clearance (Cls) (10.1–35.1 ml min-1·m-2) with the resulting mean values and standard deviations were determined. Our findings are compared with those of other authors, especially with regard to the method of detection used. This comparison indicates similar individual deviations and shorter half-lives with increasing specificity of the employed assay. Four patients studied on 3 consecutive days and, in one instance, during two different cycles of chemotherapy showed no sign of accumulation or of accelerated excretion of etoposide. There was little intrapatient variability. The pharmacokinetic parameters were correlated to clinical and laboratory findings. Statistical analysis indicated that the AUC was increased by prior cisplatin therapy and in patients with elevated levels of alkaline phosphatase. The Cls was decreased by prior cisplatin therapy, in obese patients, and by elevated alkaline phosphatase. The t1/2β of etoposide was increased in older patients. Linear regression analysis yielded a grater Vdss in patients with lower serum albumin levels, but this correlation has not yet been found to be statistically significant.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Allen LM, Creaven PJ (1975) Comparison of the human pharmacokinetics of VM26 and VP16, two antineoplastic epipodophyllotoxin glucopyranoside derivatives. Eur J Cancer 11: 697
Arbuck SG, Douglas HO, Goodwin P, Nava H, Clark J, Crom WR, Evans WE (1985) Pharmacokinetics of etoposide (VP) in patients with normal and abnormal liver function. Proc ASCO 4: 40
Creaven PJ (1982) The clinical pharmacology of VM26 and VP16-213. A brief overview. Cancer Chemother Pharmacol 7: 133
Danigel H, Pflüger KH, Jungclas H, Schmidt L, Dellbrügge J (1985) Drug monitoring of etoposide (VP16-213). I. A combined method of liquid chromatography and mass spectrometry. Cancer Chemother Pharmacol 15: 121
Evans WE, Sinkule JA, Crom WR, Dow L, Look AT, Rivera G (1982) Pharmacokinetics of teniposide (VM26) and etoposide (VP16-213) in children with cancer. Cancer Chemother Pharmacol 7: 147
Evans WE, Sinkule JA, Crom WR, Dow L, Look T, Horvath A, Tivera G (1982) Pharmacokinetics of etoposide (VP16) in children with leukemia. Chemioterapia 1: 2
Farina P, Marzillo G, D'Incalci M (1981) High-performance liquid chromatography determination of VP16-213 in human plasma. J Chromatogr 222: 141
Hande KR, Wedlung PJ, Noone RM, Wilkinson GR, Greco FA, Wolff SN (1984) Pharmacokinetics of high-dose etoposide (VP16-213) administered to cancer patients. Cancer Res 44: 379
Harvey VJ, Slevin ML, Joel SP, Johnston A, Wrigley PFM (1985) The effect of food and concurrent chemotherapy on the bioavailability of oral etoposide. Br J Cancer 52: 363
Harvey VJ, Slevin ML, Joel SP, Smythe MM, Johnston A, Wrigley PFM (1985) Variable bioavailability following repeated oral doses of etoposide. Eur J Cancer Clin Oncol 21: 1315
Holthuis JJM, Römkens FMGM, Pinedo HM, Oort WJ van (1983) Plasma assay of the antineoplastic agent VP16-213 (etoposide) using high-performance liquid chromatography with electrochemical detection. J Pharmaceut Biomed Anal 1: 89
D'Incalci M, Farina P, Sessa C, Mangioni C, Conter V, Masera G, Rocchetti M, Pisioni MB, Piazza E, Beer M, Cavalli F (1982) Pharmacokinetics of VP16-213 given by different administration methods. Cancer Chemother Pharmacol 7: 141
D'Incalci M, Farina P, Sessa C, Molina P, Mangioni C, Jancovich M, Masera G, Beer M, Cavalli F (1982) Pharmacokinetic of VP16 in humans. Chemoterapia 1: 2
D'Incalci M, Sessa C, Rossi C, Roviaro G, Mangioni C (1985) Pharmacokinetics of etoposide in gestochoriocarcinoma. Cancer Treat Rep 69: 69
D'Incalci M, Rossi C, Sessa C, Urso R, Zucchetti M, Farina P, Mangioni C (1985) Pharmacokinetics of teniposide in patients with ovarian cancer. Cancer Treat Rep 69: 73
Pelsor FR, Allen LM, Creaven PJ (1978) Multicompartment pharmacokinetic model of 4′-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-β-D-glucopyranoside) in humans. J Pharmaceut Sci 67: 1108
Postmus PE, Holthuis JJM, Haaxma-Reiche H, Mulder NH, Vencken LM, van Oort WJ, Sleijfer DT, Sluiter HJ (1984) Penetration of VP16-213 into Cerebrospinal Fluid After High-Dose Intravenous Administration. J Clin Oncol 2: 215
Sinkule JA, Stewart CF, Crom WR, Melton ET, Dahl GV, Evans WE (1984) Teniposide (VM26) disposition in children with leukemia. Cancer Res 44: 1235
Sinkule JA, Hutson P, Hayes FA, Etcubanas E, Evans W (1984) Pharmacokinetics of etoposide (VP16) in children and adolescents with refractory solid tumors. Cancer Res 44: 3109
Smyth RD, Pfeffer M, Scalzo A, Comis RL (1985) Biovailability and pharmacokinetics of etoposide (VP16). Sem Oncol XII: 48
Stewart DJ, Richard MT, Hugenholtz H, Dennery JM, Belanger R, Gerin-Lajoie J, Montpetit V, Nundy D, Prior J, Hopkins HS (1984) Penetration of VP16 (etoposide) into human intracerebral tumors. J Neuro-Oncol 2: 133
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pflüger, KH., Schmidt, L., Merkel, M. et al. Drug monitoring of etoposide (VP16-213). Cancer Chemother. Pharmacol. 20, 59–66 (1987). https://doi.org/10.1007/BF00252961
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00252961