Higher in vivo protein binding of etoposide in children compared with adult cancer patients.
Etoposide is bound to plasma albumin (94%). Previous studies have revealed altered protein binding of etoposide in cancer patients. This has clinical implications since only the free fraction is considered pharmacologically active. We have studied the etoposide protein binding in 11 children (eight acute lymphocytic leukemia, two malignant histiocytosis, and one oligodendroglioma; age 1-17 years) and 46 adult patients (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/m2 i.v. or orally. Plasma from ten healthy volunteers, 26-50 years of age, was spiked with etoposide, 10 micrograms/ml, and the protein binding was compared with that in patient samples. The free etoposide concentration was determined by high performance liquid chromatography (HPLC) after ultrafiltration at room temperature. 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 that children have significantly lower levels of free etoposide compared 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 well as cellular uptake of the drug.
Liliemark
E
E
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
Söderhäll
S
S
Sirzea
F
F
Gruber
A
A
Osby
E
E
Björkholm
M
M
Zhou
R
R
Peterson
C
C
Liliemark
J
J
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood* / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000097:blood / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D005047:Etoposide / Q000097:blood* / Q000627:therapeutic use*; D005260:Female; D054747:Histiocytic Sarcoma / Q000097:blood / Q000188:drug therapy; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy; D008223:Lymphoma / Q000097:blood / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy; D009837:Oligodendroglioma / Q000097:blood / Q000188:drug therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy; D011485:Protein Binding; D012016:Reference Values; D012709:Serum Albumin / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D012709:Serum Albumin; D005047:Etoposide