Methods for extracting neutrophil serine proteases and treating dipeptidyl peptidase 1-mediated conditions

A method of treating a DPP1-mediated condition in a patient in need thereof, comprising:

• (a) measuring a baseline concentration of an active form of one or more NSPs extracted from a first sample comprising white blood cells obtained from the patient,
• (b) orally administering to the patient daily for a first administration period of about 2 weeks to about 16 weeks, a pharmaceutical composition comprising a first daily dosage of about 10 mg to about 40 mg of a compound of formula (I), or a pharmaceutically acceptable salt thereof,
• wherein,
• R1 is
• R2 is hydrogen, F, Cl, Br, OSO2C1-3alkyl, or C1-3alkyl;
• R3 is hydrogen, F, Cl, Br, CN, CF3, SO2C1-3alkyl, CONH2 or SO2NR4R5, wherein R4 and R5 together with the nitrogen atom to which they are attached form an azetidine, pyrrolidine or piperidine ring;
• X is O, S or CF2;
• Y is O or S;
• Q is CH or N;
• R6 is C1-3alkyl, wherein the C1-3alkyl is optionally substituted by 1, 2 or 3 F and optionally by one substituent selected from OH, OC1-3alkyl, N(C1-3alkyl)2, cyclopropyl, or tetrahydropyran;
• and
• R7 is hydrogen, F, Cl or CH3;
• (c) measuring a concentration of the active form of the one or more NSPs extracted from a second sample comprising white blood cells, wherein the second sample is obtained from the patient during the first administration period, or about one week or less subsequent to the first administration period,
• (d) comparing the concentration from the second sample with the baseline concentration from the first sample;
• and
• if the concentration from the second sample is reduced by about 10% or more as compared to the baseline concentration from the first sample, then orally administering to the patient daily for a second administration period the same daily dosage as the first daily dosage of the compound of formula (I), or a pharmaceutically acceptable salt thereof, or
• if the concentration from the second sample is not reduced by about 10% or more as compared to the baseline concentration from the first sample, then orally administering to the patient daily for a second administration period a second daily dosage of the compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein the second daily dosage is about 1.5 times to about 7 times the first daily dosage.