Changes in the pharmacokinetics of PKC412 and patient mast cell disease-related parameters during PKC412 therapy. (A) Trough plasma concentration-time profiles of PKC412 and its major active metabolite CGP62221 and the sum of PKC412 and CGP62221 in the mast cell leukemia patient receiving PKC412 100 mg twice a day between day 1 and day 90, and 75 mg three times a day starting from day 90. (B) Serum histamine level and percent peripheral blood mast cells quantified by manual differential. (C) Normalized phospho-KIT/total KIT optical density ratio. The number of samples analyzed at each time point is shown in parentheses. (D) Semiquantitative DHPLC determination of the D816V KIT mutation frequency in the bone marrow and peripheral blood.