A Pharmacokinetic & Pharmacodynamic Study of Oral Lenalidomide in Patients with Low- or Intermediate-1-Risk Myelodysplastic Syndromes.

Abstract

Twelve patients diagnosed with low- or intermediate-1-risk myelodysplastic syndromes (MDS) were administered a single, 10 mg dose of lenalidomide followed by 24-hour blood and urine sampling on one occasion, and again at Day 14 of multiple dosing, followed by 5-hours of blood and urine sampling. Patients then continued into a combined treatment phase in which recombinant EPO was administered with lenalidomide. Table 1 describes the pharmacokinetic profiles of lenalidomide found for the first 12 MDS patients.Following the single oral 10 mg dose, lenalidomide had an average renal clearance of 7.48 ± 1.74 L/hr. Greater than half of the dose (65.6% ± 6.9%) was excreted unchanged in the urine over 24 hours.Conclusions: Among these MDS patients, the single and multiple dose pharmacokinetics of lenalidomide were similar, suggesting no accumulation of lenalidomide with multiple dosing. After 24 hours, 65.6% of the dose is eliminated in the urine as the parent compound. No relationship was apparent between the total number of adverse events normalized per day or Grade's 3+4 adverse events and the drug exposure.Table 1Pharmacokinetics (Mean ± SD) in MDS Patients After a Single and Multiple 10 mg Oral Dose of LenalidomideParameterSingle DoseMultiple DoseCmax1188 ± 59.5168 ± 55.4AUCt852.3 ± 272NAAUCss,0–5NA553.1 ± 205.6T½,z3.72 ± 0.75NAtmax1,21.00 (0.5, 2.00)0.75 (0.75, 2.50)1Cmax and tmax are presented on Day 142median (min, max); NA = Not Applicable