Table 3.

Population pharmacokinetic parameters of dorzagliatin and bootstrap results

Parameter	Parameter description	Final model		Bootstrap estimates median (2.5th–97.5th)
		Estimate (%RSE)	95% CI
CL/F (L/h)	Apparent total clearance	10.4 (0.923)	10.2–10.6	10.4 (10.2−10.6)
Vc/F (L)	Apparent volume of central compartment distribution	80.6 (1.23)	78.7–82.6	80.6 (77.7−83.1)
Q/F (L/h)	Inter-compartmental clearance	3.02 (9.70)	2.50–3.66	3.01 (2.29−4.14)
Vp/F (L)	Apparent volume of peripheral compartment distribution	26.5 (6.95)	23.1–30.4	26.7 (22.8−31.0)
Ka (h−1)	Absorption rate	3.29 (5.30)	2.96–3.65	3.29 (2.94−3.64)
D1 (h)	Duration of zero-order absorption	0.418 (7.49)	0.361–0.484	0.415 (0.322−0.485)
CLSTUDY	Influence of study on CL/F	1.23 (2.39)	1.17–1.28	1.22 (1.17−1.28)
D1,FOOD	Influence of food consumption time on CL/F	2.26 (12.8)	1.76–2.91	2.28 (1.85−3.10)
CLBW	Influence of body weight on CL/F	0.255 (19.4)	0.158–0.352	0.254 (0.161−0.351)
Vc,BW	Influence of body weight on Vc/F	0.553 (9.94)	0.445–0.661	0.553 (0.446−0.667)
CLAST	Influence of AST on CL/F	− 0.103 (21.3)	− 0.146 to − 0.0601	− 0.102 (− 0.149 to − 0.0589)
CLAGE	Influence of AGE on CL/F	− 0.135 (28.5)	− 0.211 to − 0.0599	− 0.133 (− 0.215 to − 0.0564)
Vc,GEND	Influence of sex on Vc	0.843 (1.74)	0.815−0.873	0.843 (0.813−0.870)
IIV_CL	IIV on CL	22.5 (2.65)	21.3−23.6	22.4 (21.0−24.0)
IIV_Vc	IIV on Vc	14.9 (5.56)	13.1−16.4	14.8 (13.0−16.5)
IIV_Vp	IIV on Vp	48.8 (9.25)	38.9−57.0	48.5 (40.6−57.1)
IIV_D1	IIV on D1	82.8 (8.16)	68.3−95.2	81.8 (65.8−98.4)
Cor_CL,Vc	Covariance (CL, Vc)	0.0181 (10.9)	0.0142−0.022	0.0181 (0.0136−0.023)
σ1 (%)	Proportional error	32.9 (1.34)	32.0−33.7	32.8 (31.2−34.5)
σ2 (ng/mL)	Additive error	109 (1.38)	106−112	109 (103−115)

IIV for CL, V_c, V_p, D₁, and proportional error are reported as approximate CV%

AGE age, AST aspartate aminotransferase, BW body weight, D₁ duration of zero-order absorption, GEND sex, IIV interindividual variability, Vc volume of central compartment, V_p volume of peripheral compartment

Parameter covariate relations were described as:

$CL/F(L/h)=10.4\times exp(0.203\times \mathrm{Study}+0.255\times \log \left(\frac{\mathit{BW}}{69}\right)-0.103\times \log \left(\frac{\mathit{AST}}{18}\right)-0.135\times \log \left(\frac{\mathit{AGE}}{55}\right)+{\eta }_{\mathit{CLi}})$

$V_{\text{c}}/F\left(L\right)=80.6\times exp\left(0.553\times log\left(\frac{\mathit{BW}}{69}\right)-0.170\times GEND+{\eta }_{\mathit{Vci}}\right)$

$D_1(h)=0.418\times \exp (0.816\times \mathrm{FOOD}+{\eta }_{D1i})$

Study: 1 for study 102/103/110, 0 for others; GEND: 1 for female, 0 for male; FOOD: 0 and 1 for the time of food consumption after 0.5 h and ≥ 1 h of drug administration, respectively

The shrinkage of CL/F, V_c/F, V_p/F and D1 are 22.5%,14.9%, 48.8% and 82.8%, respectively