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 1.

Pharmacokinetics (Mean ± SD) in MDS Patients After a Single and Multiple 10 mg Oral Dose of Lenalidomide

ParameterSingle DoseMultiple Dose
1 Cmax and tmax are presented on Day 14; 2 median (min, max); NA = Not Applicable 
Cmax1 188 ± 59.5 168 ± 55.4 
AUCt 852.3 ± 272 NA 
AUCss,0–5 NA 553.1 ± 205.6 
T½,z 3.72 ± 0.75 NA 
tmax1,2 1.00 (0.5, 2.00) 0.75 (0.75, 2.50) 
ParameterSingle DoseMultiple Dose
1 Cmax and tmax are presented on Day 14; 2 median (min, max); NA = Not Applicable 
Cmax1 188 ± 59.5 168 ± 55.4 
AUCt 852.3 ± 272 NA 
AUCss,0–5 NA 553.1 ± 205.6 
T½,z 3.72 ± 0.75 NA 
tmax1,2 1.00 (0.5, 2.00) 0.75 (0.75, 2.50) 

Disclosure: No relevant conflicts of interest to declare.

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