TY - JOUR
T1 - Pharmacokinetics of temozolomide given three times a day in pediatric and adult patients
AU - Riccardi, Anna
AU - Mazzarella, Giorgio
AU - Cefalo, Graziella
AU - Garrè, Maria Luisa
AU - Massimino, Maura
AU - Barone, Carlo
AU - Sandri, Alessandro
AU - Ridola, Vita
AU - Ruggiero, Antonio
AU - Mastrangelo, Stefano
AU - Iazzareschi, Ilaria
AU - Caldarelli, Massimo
AU - Maira, Giulio
AU - Madon, Enrico
AU - Riccardi, Riccardo
PY - 2003/12
Y1 - 2003/12
N2 - Purpose: To characterize and compare pharmacokinetic parameters in children and adults treated with temozolomide (TMZ) administered for 5 days in three doses daily, and to evaluate the possible relationship between AUC values and hematologic toxicity. Methods: TMZ pharmacokinetic parameters were characterized in pediatric and adult patients with primary central nervous system tumors treated with doses ranging from 120 to 200 mg/m2 per day, divided into three doses daily for 5 days. Plasma levels were measured over 8 h following oral administration in a fasting state. A total of 40 courses were studied in 22 children (mean age 10 years, range 3-16 years) and in 8 adults (mean age 30 years, range 19-54 years). Results: In all patients, a linear relationship was found between systemic exposure (AUC) and increasing doses of TMZ. Time to peak concentration, elimination half-life, apparent clearance and volume of distribution were not related to TMZ dose. No differences were seen among TMZ Cmax, t1/2, Vd or CL/F in children compared with adults. Intra- and interpatient variability of systemic exposure were limited in both children and adults. No statistically significant differences were found between the AUCs of children who experienced grade 4 hematologic toxicity and children who did not. Conclusions: No difference appears to exist between pharmacokinetic parameters in adults and children when TMZ is administered in three doses daily. Hematologic toxicity was not related to TMZ AUC. AUC measurement does not appear to be of any use in optimizing TMZ treatment.
AB - Purpose: To characterize and compare pharmacokinetic parameters in children and adults treated with temozolomide (TMZ) administered for 5 days in three doses daily, and to evaluate the possible relationship between AUC values and hematologic toxicity. Methods: TMZ pharmacokinetic parameters were characterized in pediatric and adult patients with primary central nervous system tumors treated with doses ranging from 120 to 200 mg/m2 per day, divided into three doses daily for 5 days. Plasma levels were measured over 8 h following oral administration in a fasting state. A total of 40 courses were studied in 22 children (mean age 10 years, range 3-16 years) and in 8 adults (mean age 30 years, range 19-54 years). Results: In all patients, a linear relationship was found between systemic exposure (AUC) and increasing doses of TMZ. Time to peak concentration, elimination half-life, apparent clearance and volume of distribution were not related to TMZ dose. No differences were seen among TMZ Cmax, t1/2, Vd or CL/F in children compared with adults. Intra- and interpatient variability of systemic exposure were limited in both children and adults. No statistically significant differences were found between the AUCs of children who experienced grade 4 hematologic toxicity and children who did not. Conclusions: No difference appears to exist between pharmacokinetic parameters in adults and children when TMZ is administered in three doses daily. Hematologic toxicity was not related to TMZ AUC. AUC measurement does not appear to be of any use in optimizing TMZ treatment.
KW - Brain tumors pharmacokinetics
KW - Chemotherapy
KW - Children
KW - Temozolomide
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U2 - 10.1007/s00280-003-0677-x
DO - 10.1007/s00280-003-0677-x
M3 - Article
C2 - 13680160
AN - SCOPUS:0345375541
VL - 52
SP - 459
EP - 464
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
IS - 6
ER -