HIGHER IN-VIVO PROTEIN-BINDING OF ETOPOSIDE IN CHILDREN COMPARED WITHADULT CANCER-PATIENTS

Etoposide is bound to plasma albumin (94%). Previous studies have reve aled altered protein binding of etoposide in cancer patients. This has clinical implications since only the free fraction is considered phar macologically active, We have studied the etoposide protein binding in 11 children (eight acute lymphocytic leukemia, two malignant histiocy tosis, and one oligodendroglioma; age 1-17 years) and 46 adult patient s (28 acute myelocytic leukemia, eight lymphoma, one multiple myeloma, and nine small cell lung cancer; age 38-81 years). All patients were treated with etoposide 50-200 mg/m(2) i.v. or orally. Plasma from ten healthy volunteers, 26-50 years of age, was spiked with etoposide, 10 mu g/ml, and the protein binding was compared with that in patient sam ples. The free etoposide concentration was determined by high performa nce liquid chromatography (HPLC) after ultrafiltration at room tempera ture, The free etoposide fraction was lower, 2.5 +/- 0.6% (mean +/- SD ), in the children compared with 5.0 +/- 3.6% in adult cancer patients , In plasma from healthy adults it was 3.2 +/- 0.3%. It is concluded t hat children have significantly lower levels of free etoposide compare d with adult patients (P = 0.03) as well as with healthy subjects (P = 0.001), which is likely to affect metabolism and renal clearance as w ell as cellular uptake of the drug.