A phase I dose-escalation study of PEP02 (irinotecan liposome injection) in combination with 5-fluorouracil and leucovorin in advanced solid tumors

Table 4 Pharmacokinetic parameters of PEP02 at each dose level

	Dose of PEP02 (mg/m²)	C _max CPT-11 (μg/mL) SN-38 (ng/mL)	T _max (hr)	AUC_0→169.5 CPT-11 (hr-μg/mL) SN-38 (hr-ng/mL)	AUC_0→∞ CPT-11 (hr-μg/mL) SN-38 (hr-ng/mL)	V _ss (L/m²)	Cl (mL/hr/m²)	t _1/2 (hr)
Total CPT-11	60, N = 3	28.9 ± 15.8	2.4 ± 0.7	1047 ± 1210	1047 ± 1210	2.80 ± 1.59	136 ± 116	21.1 ± 11.7
	80, N = 6	29.2 ± 5.2	2.1 ± 0.7	1096 ± 834	1151 ± 880	3.39 ± 0.74	124 ± 106	33.3 ± 15.1
	100, N = 5	44.1 ± 7.7	4.0 ± 3.8	2237 ± 1090	2289 ± 1119	2.86 ± 0.75	58 ± 37	43.17 ± 4.8
	120, N = 2	47.9 ± 16.2	2.3 ± 0.9	1254 ± 553	1254 ± 553	3.95 ± 0.83	106 ± 47	54.4 ± 17.4
SN-38	60, N = 3	7.02 ± 5.64	13.1 ± 11.7	364 ± 222	1370 ± 1122	NA	NA	183.8 ± 172.3
	80, N = 6	7.98 ± 4.39	13.3 ± 18.3	343 ± 133	505 ± 165	NA	NA	57.5 ± 17.8
	100, N = 5	7.39 ± 1.68	12.2 ± 12.3	539 ± 368	840 ± 433	NA	NA	73.4 ± 18.3
	120, N = 2	7.26 ± 3.90	37.8 ± 17.2	353 ± 164	305	NA	NA	30.8
	Irinotecan^a	26.3 ± 11.9	NA	229 ± 108	NA	NA	NA	10.4 ± 3.1

Mean ± STD; C_max, peak concentration in plasma; T_max, time to achieve peak plasma concentration; AUC_0→169.5 and AUC_0→∞, area under the plasma concentration-time curve from time zero to 169.5 h and infinity, respectively; V_ss, volume of distribution at steady state; t_1/2, plasma terminal elimination half-life; Cl, total clearance of drug from plasma; NA, not available
^aIrinotecan 125 mg/m², package inset of Campto^®