Variability in teniposide plasma protein binding is correlated with serum albumin concentrations.
Teniposide is a widely used anticancer drug that is extensively bound to plasma proteins (greater than 95%). We evaluated the drug's plasma protein binding in nine patients with acute lymphocytic leukemia who were in their first complete remission, and in a second group of nine patients at the time of relapse and subsequently after achieving another complete remission. Plasma protein binding was assessed by equilibrium dialysis, with direct high-performance liquid chromatographic measurement of total and free teniposide. The mean unbound fraction was 0.44% (0.21-0.88%) in the plasma of patients in first remission. It was significantly higher in patients at the time of relapse (mean = 0.86%; range 0.68-1.08%) and after achieving another complete remission (mean = 1.25%; range 0.51-2.11%). Serum albumin values were significantly lower at the time of relapse (mean = 4.6 vs 4.0 mg/dl; p less than 0.014), and decreased further during intensive postremission therapy containing L-asparaginase (mean = 3.2; p less than 0.05). For all 18 patients, a significant negative correlation (r2 = 0.667; p less than 0.001) was found between serum albumin and unbound teniposide, with low albumin being associated with higher unbound fraction. Such patients have higher systemic exposure to unbound (presumably active) teniposide at any given total plasma concentration of the agent.
Petros
W P
WP
Pharmaceutical Division, St. Jude Children's Research Hospital, Memphis, TN 38105.
Rodman
J H
JH
Relling
M V
MV
Christensen
M
M
Pui
C H
CH
Rivera
G K
GK
Evans
W E
WE
D000293:Adolescent; D000328:Adult; D001798:Blood Proteins / Q000378:metabolism*; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism*; D011485:Protein Binding; D012074:Remission Induction; D012709:Serum Albumin / Q000032:analysis*; D013713:Teniposide / Q000378:metabolism* / Q000627:therapeutic use
D001798:Blood Proteins; D012709:Serum Albumin; D013713:Teniposide