Table 6.

Pharmacokinetic variabilities of NASH group compared with control group and judgment of related influencing factors.

Drugs	PK changes (ig)		PK changes (iv)		Cyp450s changes		AUCmetabolite/AUCparent drug		Gut microbiota	Main influencing factors
	Parent drug	Metabolite	Parent drug	Metabolite	Activity	Expression	ig	iv	Biotransformation	Host/gut microbiota
Omeprazole	AUC↑, CLz/F↓	AUC↓, Cmax ↓, t1/2↓	AUC(0-12h)↑	−	Cyp2c29↓	Cyp2c29↓	↓	↓	Yes	gut microbiota
Phenacetin	AUC↑, Cmax ↑,CLz/F↓	AUC↑, t1/2 ↓, CLz/F↓	−	AUC(0-12h)↑	Cyp1a2↓	Cyp1a2↓	−	−	Yes	gut microbiota
Midazolam	AUC↑, Cmax ↑,CLz/F↓	AUC↑, Cmax ↑, Tmax ↑, t1/2↑, CLz/F↓	−	AUC↑, Cmax ↑,CLz/F↓	Cyp3a11↓	Cyp3a11↓	−	−	Yes	gut microbiota
Chlorzoxazone	AUC↑, Cmax ↑,CLz/F↓	−	−	−	Cyp2e1−	Cyp2e1↓	−	−	Yes	gut microbiota
Tolbutamide	AUC↑, Cmax ↑, Tmax ↑ t1/2↑, CLz/F↓	AUC↑, Cmax ↑, Tmax ↑, t1/2↑	AUC↑, t1/2↑,CLz/F↓	AUC↑, Cmax ↑, Tmax ↑,CLz/F↓	Cyp2c65↓	Cyp2c65↓	↓	↓	No	host
Metoprolol	−	−	−	−	Cyp2d22−	Cyp2d22−	−	−	No	Neither

Note: The results in the table are from the NASH group vs. the control group in mice. −: not significant. ↑: significantly increased. ↓: significantly decreased. ig: intragastric administration. iv: intravenous administration. Based on the results of Cyp450 enzymes in vitro as the standard, combined with the results of Cyp450 enzymes in vivo, their relationships can be roughly divided into three categories: 1) if the results were consistent, the pharmacokinetic variabilities were mainly related to the host alteration; 2) if the results were inconsistent, the pharmacokinetic variabilities were mainly related to the gut microbiota; and 3) if the results did not change, the pharmacokinetics were less affected by both factors.