Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors

Table 3 Pharmacokinetic parameters of anlotinib after a single oral dose of anlotinib capsules in cancer patients and summarized results from dose proportionality assessment

Pharmacokinetic parameters	Measurement of dose-dependent pharmacokinetics				Assessment of dose proportionality
Pharmacokinetic parameters	5 mg/person (n = 1)	10 mg/person (n = 4)	12 mg/person (n = 11)	16 mg/person (n = 4)	r	P	Slope (90 % CI)	Conclusion
C _max, ng/mL	5.8	5.8 ± 2.8	10.5 ± 2.9	15.8 ± 3.2	0.629	0.003	1.12 (0.54–1.71)	Inconclusive
T _max, h	11.0	6.0 ± 4.4	7.3 ± 3.3	11.0 ± 8.9	–	–	–	–
AUC_0–120h, h·ng/mL	411	318 ± 133	617 ± 194	894 ± 305	0.465	0.045	0.81 (0.16–1.45)	Inconclusive
AUC_0–∞, h·ng/mL	687	562 ± 328	1066 ± 263	1585 ± 470	0.666	0.002	1.18 (0.62–1.73)	Inconclusive
t _1/2, h	102	95 ± 22	116 ± 47	98 ± 15	–	–	–	–

Critical intervals were 0.791–1.209 for the systemic exposure data of anlotinib from a single oral dose of anlotinib capsules (10–16 mg) in cancer patients. The term r denotes the correlation coefficient. Correlations were statistically significant with P < 0.05. The term “linear” was concluded statistically if the 90 % confidence interval (90 % CI) for the slope was contained completely within the critical interval; inconclusive was concluded statistically if the 90 % CI lies partly within the critical interval; nonlinear was concluded statistically if the 90 % CI was entirely outside the critical interval
C _max maximum plasma concentration, T _max the time taken to achieve the maximum plasma concentration, AUC _0–120h the area under concentration-time curve up to 120 h, AUC _0–∞ area under concentration-time curve up to infinity, t _1/2 terminal elimination half-life

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