Objective: To ascertain the role of patient age as an influencing factor in the pharmacokinetics of anagrelide and to clarify whether different dosing is required in young (18 - 50 years) vs. elderly (>= 65 years) patients with essential thrombocythemia (ET). Method: This Phase II, multicenter, open-label study compared the pharmacokinetics, pharmacodynamics and tolerability of anagrelide and its active metabolite, 3-hydroxy-anagrelide, in young and elderly patients with ET. Three days prior to pharmacokinetic assessment, patients divided their normal daily anagrelide into a structured twice-daily dosing (BID) schedule. Serial blood samples were obtained for pharmacokinetic and pharmacodynamic analysis over a 12-h dosing interval. Anagrelide and 3-hydroxy-anagrelide plasma concentrations were normalized to a common dose (1 mg BID) to control for dosing differences between patients. Patients were monitored routinely for adverse events (AEs) and vital signs. Results: A total of 24 patients (12 young; 12 elderly) completed the study. The dose-normalized anagrelide maximum observed plasma concentration (C-max) and area under the plasma concentration vs. time curve over one dosing interval (AUC(tau)), were higher in elderly patients compared with young patients (C-max: 3.63 vs. 2.66 ng/ml; p = 0.09, AUC(tau): 10.3 vs. 6.4 ngxh/ml; p = 0.01). In contrast, the dose-normalized 3-hydroxy-anagrelide C-max and AUC(tau) were lower in the elderly patients when compared with young patients (C-max: 4.19 vs. 7.26 ng/ml; p = 0.02, AUC(tau): 17.4 vs. 27.6 ngxh/ml; p = 0.03). No significant difference was observed in the geometric mean terminal half-life (t(1/2)) of anagrelide in elderly and young patients (1.4 vs. 1.3 h, respectively; p = 0.38), whereas the geometric mean t(1/2) of 3-hydroxy-anagrelide was significantly longer in the elderly patients compared with the young patients (3.5 vs. 2.7 11, respectively; p = 0.01). There were no significant differences in platelet count or vital signs between the age groups. Anagrelide was well tolerated; there were no serious AEs or AEs that led to withdrawal from the study. Conclusions: To conclude, the differences observed in anagrelide and 3-hydroxy-anagrelide pharmacokinetics do not justify using a different dosing regimen in young vs. elderly patients with ET.