Table 5.

Summary of PK parameters for pemetrexed and platinum (total and free) derived from cisplatin

Dose level 1Dose level 2Dose level 3Dose level 4Dose level 5Overall
Pemetrexed dose (mg/m2)500600700800900NA
n3336621
BSA, m2* (range)1.71 (1.43-1.91)1.58 (1.46-1.82)1.93 (1.51-2.19)1.77 (1.54-1.96)1.98 (1.88-2.08)1.82 (1.43-2.19)
Baseline CrCL, mL/min* (range)69.9 (48.3-91.4)72.6 (43.1-109)78.1 (52.5-102)99.0 (57.9-139)102 (72.3-134)89.7 (43.1-139)
Pemetrexed
    Total dose, mg* (range)870 (734-979)970 (894-1,120)1,420 (1,280-1,530)1,430 (1,200-1,580)1,820 (1,730-1,890)NA
    Cmax, μg/mL§ (CV%)113 (20)122 (9)156 (9)154 (16)180 (18)NA
    AUC0-∞, μg·h/mL§ (CV%)261 (5)188 (41)267 (37)279 (14)299 (24)NA
    CL, mL/min§ (CV%)55.3 (13)85.5 (43)88.6 (29)84.9 (14)101 (25)NA
    Vss, L§ (CV%)13.1 (34)12.8 (22)16.4 (15)13.2 (22)16.9 (20)NA
    t1/2, h§ (range)3.39 (2.74-3.78)2.91 (2.62-3.36)3.29 (2.82-4.28)2.76 (2.59-2.92)3.25 (2.63-5.20)NA
Cisplatin total dose, mg* (range)129 (110-140)120 (110-140)143 (112-160)132 (110-148)146 (140-153)135 (110-160)
    Total platinum
    Cmax, μg/mL§ (CV%)*3.48 (10)3.18 (16)3.26 (13)2.93 (10)3.21 (15)3.17 (13)
    AUC0-∞, μg·h/mL§ (CV%)*310 (19)334 (30)238 (24)287 (12)247 (13)277 (20)
    CL, L/h/m2§ (CV%)*0.244 (17)0.227 (31)0.313 (26)0.260 (14)0.299 (13)0.270 (20)
    Vss, L/m2§ (CV%)*43.6 (10)44.1 (15)48.4 (14)47.4 (14)51.4 (11)47.6 (13)
    t1/2, h§ (range)75.2 (72.3-78.1)108 (73.6-159)80.1 (71.8-87.3)88.9 (60.1-110)86.6 (69.8-111)87.2 (60.1-159)
Free platinum
    Cmax, μg/mL§ (CV%)*2.24 (40)2.35 (18)2.25 (13)1.97 (19)1.88 (27)2.07 (23)
    AUC0-∞, μg·h/mL§ (CV%)*3.45 (33)3.23 (27)3.27 (4)2.77 (16)2.61 (16)2.94 (21)
    CL, L/h/m2§ (CV%)*21.9 (30)23.5 (27)22.7 (4)27.0 (18)28.3 (17)25.4 (21)
    Vss, L/m2§ (CV%)*28.0 (3)21.5 (23)28.1 (29)23.4 (26)25.9 (20)25.1 (22)
    t1/2, h§ (range)0.845 (0.643-0.970)0.640 (0.514-0.951)1.04 (0.970-1.11)0.631 (0.476-1.00)0.768 (0.590-1.13)0.749 (0.476-1.13)
  • Abbreviations: NA, not applicable; BSA, body surface area; CrCL, creatinine clearance based on Cockcroft-Gault method; CV%, coefficient of variation as percentage.

  • * Arithmetic mean.

  • n = 2.

  • n = 20.

  • § Geometric mean.