Table 3.

In vitro metabolism, protein binding, and blood-to-plasma concentration ratio data for kratom alkaloids.

Alkaloid	t1/2,HIMs (min)	t1/2,HLMs (min)	fu,p	fu,mic	CB/CP	CLint,H (mL/min/kg)	CLH,u (mL/min/kg)
Mitragynine	45.9 ± 0.8	10.1 ± 0.2	0.039 ± 0.003	0.536 ± 0.003	0.93 ± 0.02	31.0	1.22
Speciogynine	41.7 ± 1.3	9.6 ± 0.1	0.057 ± 0.001	0.602 ± 0.009	0.65 ± 0.02	32.6	2.53
Mitraciliatine	45.6 ± 3.4	15.5 ± 0.2	0.019 ± 0.003	0.337 ± 0.006	1.05 ± 0.01	20.2	0.49
Speciociliatine	>60	26.2 ± 0.4	0.040 ± 0.003	0.509 ± 0.012	0.74 ± 0.04	11.9	0.61
Paynantheine	29.9 ± 0.3	7.5 ± 0.3	0.055 ± 0.005	0.516 ± 0.016	0.75 ± 0.01	41.9	2.67
Isopaynantheine	53.5 ± 2.9	14.7 ± 0.2	0.024 ± 0.002	0.412 ± 0.004	0.66 ± 0.02	21.2	0.73

Values represent means ± S.D. of triplicate determinations. t_1/2, in vitro half-life; HIMs, human intestinal microsomes; HLMs, human liver microsomes; f_u,p, unbound fraction in plasma; f_u,mic, unbound fraction in microsomal incubation; C_B/C_P, blood-to-plasma concentration ratio; CL_int,H, in vitro hepatic intrinsic clearance; CL_H,u, predicted unbound hepatic clearance using the well-stirred model (see Supplemental Materials for details).