ce and volume of distribution values tend to be higher in Whites (n = 63) than in Blacks (by about 10%) (n = 15). The opposite is true for ara-G; mean apparent clearance and volume of distribution values tend to be lower in Whites than in Blacks (by about 15-20%). No differences in safety or effectiveness were observed between these groups.
Geriatrics: Age has no effect on the pharmacokinetics of nelarabine or ara-G. Decreased renal function, which is more common in the elderly, may reduce ara-G clearance (see PRECAUTIONS, Geriatric Use).
Pediatrics: No pharmacokinetic data are available in pediatric patients at the once daily 650 mg/m2 nelarabine dosage. Combined Phase 1 pharmacokinetic data at nelarabine doses of 104 to 2,900 mg/m2 indicate that the mean clearance (CL) of nelarabine is about 30% higher in pediatric patients than in adult patients (259 ± 409 L/h/m2 versus 197 ± 189 L/h/m2, respectively) (n = 66 adults, n = 22 pediatric patients) on Day 1. The apparent clearance of ara-G (CL/F) is comparable between the two groups (10.5 ± 4.5 L/h/m2 in adult patients and 11.3 ± 4.2 L/h/m2 in pediatric patients) on Day 1.
Nelarabine and ara-G are extensively distributed throughout the body. Specifically, for nelarabine, VSS values were 197 ± 216 L/m2 and 213 ± 358 L/m2 in adult and pediatric patients, respectively. For ara-G, VSS/F values were 50 ± 24 L/m2 and 33 ± 9.3 L/m2 in adult and pediatric patients, respectively.
Renal Impairment: The pharmacokinetics of nelarabine and ara-G have not been specifically studied in renally impaired or hemodialyzed patients. Nelarabine is excreted by the kidney to a small extent (5 to 10% of the administered dose). Ara-G is excreted by the kidney to a greater extent (20 to 30% of the administered nelarabine dose). Patients were categorized into 3 groups: normal with CLcr >80 mL/min (n = 67), mild with CLcr = 50-80 mL/min (n = 15), and moderate with CLcr<50 mL/min (n = 3). The mean apparent clearance (CL/F) of ara-G was about 15% and 40% lower in patients with mild and moderate renal impairment, respectively, than in patients with normal renal function (see PRECAUTIONS and DOSAGE AND ADMINISTRATION). No differences in safety or effectiveness were observed.
Hepatic Impairment: The influence of hepatic impairment on the pharmacokinetics of nelarabine has not been eva luated.
Drug Interactions
Nelarabine and ara-G did not significantly inhibit the activities of the human hepatic cytochrome P450 isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4 in vitro at concentrations of nelarabine and ara-G up to 100 μM.
Administration of fludarabine 30 mg/m2 as a 30-minute infusion 4 hours before a 1,200 mg/m2 infusion of nelarabine did not affect the pharmacokinetics of nelarabine, ara-G, or ara-GTP in 12 patients with refractory leukemia.
CLINICAL STUDIES
The safety and efficacy of ARRANON were eva luated in two open-label, single-arm, multicenter studies.
Pediatric Clinical Study
The safety and efficacy of ARRANON in pediatric patients were studied in a clinical trial conducted by the Children&rsqu
