Table S1

 S1 Calibration curves for DTX in rat tissues. 


	Tissues	Slope	Intercept	r	Linear ranges
		(×10 -4 )	(×10 -3 )		(ng • g -1 )
	Lung	3.22	1.15	0.992	12.5-5.00E03
	Brain	5.27	15.3	0.994	12.5-5.00E03
	Heart	5.16	6.93	0.998	12.5-5.00E03
	Spleen	4.20	3.02	0.993	12.5-5.00E03
	Liver	5.07	9.16	0.999	12.5-5.00E03
	Intestine	4.77	17.0	0.997	12.5-5.00E03
	Kidney	5.57	15.5	0.996	12.5-5.00E03
	Muscle	5.06	11.4	0.996	12.5-5.00E03

Table S2

 S2 Summary of the covariate model-building steps.CL li : hepatic clearance; K t, br : partition coefficient for brain; K t, gu : partition coefficient for gut; K t, he : partition coefficient for heart; K t, ki : partition coefficient for kidney; K t, li : partition coefficient for liver; K t, lu : partition coefficient for lung; K t, mu : partition coefficient for muscle; K t, re : partition coefficient for the remainder compartment; K t, sp : partition coefficient for spleen; K t, pl : blood-to-plasma partition coefficient.∆IIV represents the variation of inter-individual variability.∆OFV represents the variation of objective function value.Effects of dosage form and sex on DTX PBPK parameters. CL gu : gut clearance; F: female; INJ: simple DTX injection; K t, br : partition coefficient for brain; K t, he : partition coefficient for heart; K t, ki : partition coefficient for kidney; K t, li : partition coefficient for liver; K t, lu : partition coefficient for lung; K t, mu : partition coefficient for muscle; K t, re : partition coefficient for the remainder compartment; K t, sp : partition coefficient for spleen; K t, pl : blood-to-plasma partition coefficient; FA: FA-PEG-PCHL-modified liposomes; M: male. The boxes represent the 25th, 50th and 75th percentiles; the whiskers represent the lowest datum still within 1.5 interquartile ranges (IQRs) of the lower quartile, and the highest datum still within 1.5 IQRs of the upper quartile range; the solid circles represents outliers. ETA represents the relative errors based on the typical values of PBPK parameters. 


	sex on K t, lu sex on K t, he sex on CL gu dosage form on K t, ki dosage form on K t, re CL gu : intestinal clearance; Figure S1.	-5.12 -9.60 -25.9 -39.5 -27.6	-19.2 -33.0 -66.1 -80.7 -68.3
	Effect of covariates sex on CL li dosage form on K t, mu	Parameter variation -6.58 -7.94	-24.0 -28.2
	sex on K t, gu dosage form and sex on K t, re	∆OFV -3.87 -33.3	∆IIV (%) -14.9 -75.0
	Forward selection sex on CL gu Final model	-25.9	-66.1
	dosage form on K t, pl sex on K t, re dosage form on K t, pl	-17.9 -4.77 -17.9	-52.7 -18.0 -52.7
	dosage form on K t, lu Full-covariate model dosage form on K t, lu	-12.1 -12.1	-39.7 -39.7
	dosage form on K t, br dosage form on K t, pl dosage form on K t, br	-11.2 -17.9 -11.2	-37.4 -52.7 -37.4
	dosage form on K t, sp dosage form and sex on K t, lu sex on K t, he	-24.0 -17.7 -9.60	-63.1 -52.1 -33.0
	dosage form on K t, li dosage form on K t, br dosage form on K t, sp	-18.1 -11.2 -24.0	-52.9 -37.4 -63.1
	dosage form on K t, gu sex on K t, he dosage form on K t, li	-4.72 -9.60 -18.1	-17.9 -33.0 -52.9
	dosage form on K t, ki dosage form on K t, sp sex on CL gu	-39.5 -24.0 -25.9	-80.7 -63.1 -66.1
	dosage form on K t, mu dosage form on K t, li dosage form on K t, ki	-7.94 -18.1 -39.5	-28.2 -52.9 -80.7
	dosage form on K t, re sex on CL li dosage form on K t, mu	-27.6 -6.58 -7.94	-68.3 -24.0 -28.2
	dosage form and sex on K t, gu	-8.56	-30.0