TABLE 1

Primary pharmacokinetic parameters of radioactivity and capmatinib in blood and plasma (based on noncompartmental analysis)

Values are shown as meana (S.D.) for N = 6 volunteers unless mentioned otherwise.

PK ParameterBlood RadioactivityPlasma RadioactivityPlasma Capmatinib
Tmax [h] (median; range)2; 1 to 22; 1 to 22; 1 to 2
Cmax [ng/ml]b7300 (2880)7850 (3840)3670 (1710)
Tlast [h] (range)24–4824–4824–72
AUClast [ng·h/ml]c,d47,400 (13,700)43,800 (16,400)14,300 (5330)
t1/2 [h]8.5 (4.8)10.6 (4.0)7.8 (3.1)
AUCinfe [ng·h/ml]c,d [% of14C-AUCinf plasma]49,700 (13,400)45,500 (15,900)14,400 (5310)
114.3 (17.6)31.5 (2.9)
AUC%Extrap [% of AUCinf]5.3 (3.9)5.0 (4.5)0.5 (0.6)
Vz/F [l]624 (511)
CL/F [l/h]51.7 (34.4)
  • NA, not applicable; PK, pharmacokinetic; Tlast, time point corresponding to the last measurable concentration; t1/2, half-life; –, not calculable/not meaningful.

  • a Mean values are arithmetic means of individual values.

  • b For radioactivity: [ng-eqper ml].

  • c For radioactivity: [ng-eq·h per ml].

  • d AUClast were calculated using the linear trapezoidal rule. The typical time interval was 8–24 h for blood radioactivity and 12–48 h for plasma radioactivity and plasma capmatinib.

  • e AUCinf = AUClast + AUCt-inf; AUCt-inf = Clast * t1/2/ln2. Eq, equivalent; Extrap, extrapolated; AUCt-inf; AUC from tlast to infinity.