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 C(max), t(1/2), V(d) 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.
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 C(max), t(1/2), V(d) 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.
Authors: A Ruggiero; G Cefalo; M L Garré; M Massimino; C Colosimo; G Attinà; I Lazzareschi; P Maurizi; V Ridola; G Mazzarella; M Caldarelli; C Di Rocco; E Madon; M E Abate; A Clerico; A Sandri; R Riccardi Journal: J Neurooncol Date: 2006-03 Impact factor: 4.130
Authors: U Bartels; S Baruchel; A S Carret; B Crooks; J Hukin; D Johnston; M Silva; D Strother; B Wilson; S Zelcer; D Eisenstat; L Sung; E Bouffet Journal: Curr Oncol Date: 2011-01 Impact factor: 3.677
Authors: A Laura Nijstad; Shelby Barnett; Arief Lalmohamed; Inez M Bérénos; Elizabeth Parke; Vickyanne Carruthers; Deborah A Tweddle; Jordon Kong; C Michel Zwaan; Alwin D R Huitema; Gareth J Veal Journal: Eur J Cancer Date: 2021-12-02 Impact factor: 9.162
Authors: Antonio Ruggiero; Anna Ariano; Silvia Triarico; Michele Antonio Capozza; Alberto Romano; Palma Maurizi; Stefano Mastrangelo; Giorgio Attinà Journal: Drugs Context Date: 2020-06-02