Table 2.

Main pharmacokinetic parameters of anti-tubulin agents in humans

Drug	t1/2	Cl(tot)	Vd	BBB	P-gp	Metabolism	Ref.
Vinblastine	25 (23-85) h	0.74 L/h/kg (863 mL/min)	27.3 L/kg (2,047 L)	-	+	CYP3A41	[74]
Vincristine	23-85 h	146 mL/min	215 L	-	+	CYP3A4/52	[75]
Vindesine	20-24 h	NA	8.11 L/kg (608 L)	-	+	CYP3A42	[76]
Vinorelbine	28-44 h	0.97-1.26 L/h/kg (1,280-1,680 mL/min)	25.4-40.1 L/kg (1,905-3,007 L)	+	+	CYP3A3	[77]
Vincristine Liposomal	7.7 ± 3.2 h	345 ± 177 (148-783) mL/h (6 ± 3 mL/min)	Vd = 3.6 ± 1.9 L Vdss = 2.9 ± 1.2 L	-	+	CYP3A42	[41]
Vinflunine	40 h	40 L/h (667 mL/min)	2,422 ± 676 L	-	+	Esterases, CYP3A42	[78]
Paclitaxel*	13-53 h	12.2-23.8 L/h/m2 (351-685 mL/min)	227-688 L/m2 (392-1,190 L)	-	+	CYP2C8, CYP3A42	[79]
Docetaxel	11 h	21 L/h/m2 (605 mL/min)	113 L	-	+	CYP3A4/5	[79]
Nab-Paclitaxel	27 h	15 L/h/m2 (432 mL/min)	632 L/m2 (1,093 L)	-	+	CYP2C8, CYP3A4	[79]
Cabazitaxel	95 h	48.5 L/h (761 mL/min)	4,864 L	(+)	(-)	CYP2C8, CYP3A4, CYP3A54	[79]
Patupilone	137 ± 70 h	14.0 ± 5.3 L/h (233 ± 88 mL/min)	224,2 ± 926 L	+	-	Esterases, CYP3A4/3A	[80]
Ixabepilone	35/52 h	616 mL/min	21-26 L/kg (1,575-1,950 L)	+	-	CYP2D6, CYP2C19, CYP3A4, CYP3A52	[81]
Sagopilone	53 h	1,359 mL/min	4,607 L	+	-	Esterases, CYP3A4/3A, CYP2C192	[62]
KOS-862	9.1 ± 2.2 h	9.3 ± 3.2 L/h/m2 (155 ± 53 mL/min/m2 = 268 ± 92 mL/min)	119 ± 41 L/m2 (206 ± 71 L)	+	-	CYP3A4, CYP2C9, CYP2C19, CYP2B62	[82]
KOS-1584	21.9 ± 8.8 h	11 ± 6.2 L/h/m2 (183 ± 103 L/min/m2 = 317 ± 178 mL/min)	327 ± 161 L/m2 (566 ± 279 L)	+	-	CYP3A42	[83]

*non-linear pharmacokinetics characterized by a disproportionately large increase in Cmax and AUC with increasing dose. Active metabolite(s): ¹Desacetylvinblastine; ²not described; ³desacetylvinorelbine; ⁴N = 3, one of them docetaxel. t_1/2: Terminal half-life; Vdss: volume of distribution at steady state; Vd: volume of distribution; Cl(tot): total plasma clearance; BBB: passage of the blood-brain barrier; P-gp: resistance due to P-gp overexpression. Assumptions for conversions: BMI = 1.73 m², BM = 75 kg