Effect of Dan-Lou tablets on the pharmacokinetics and pharmacodynamics of atorvastatin in high-fat diet-fed rats

doi:10.12092/j.issn.1009-2501.2026.03.004

Abstract

Abstract:

AIM: To investigate the effects of Dan-Lou tablets (DLT) on the pharmacokinetics and pharmacodynamics of atorvastatin (ATV) in hyperlipidemic rats, and provide theoretical basis for clinical combination therapy of Chinese and Western medicines in dyslipidemia management. METHODS: A high-fat diet-induced hyperlipidemic rat model was established. Following single and multiple oral administrations of DLT at clinical equivalent doses combined with ATV, plasma concentrations of ATV and its active metabolites were quantified using LC-MS/MS with multiple reaction monitoring (MRM) mode. Pharmacokinetic parameters were calculated through non-compartmental analysis. Pharmacodynamic evaluations included serum lipid profiles (TC, TG, HDL-C, LDL-C) and histopathological examination of hepatic tissue. RESULTS: Pharmacokinetic analysis revealed that compared with ATV monotherapy, DLT co-administration increased AUC_0-24h by 160.63% and 50.96% in normal and model groups, respectively, with corresponding C_max elevations of 27.95% and 7.93%. Pharmacodynamically, the combination therapy demonstrated superior effects with 29.89% body weight reduction versus 12.48% in ATV monotherapy group. Significant improvements were observed in lipid profiles: TC, TG and LDL-C decreased by 38.2%, 41.7% and 52.4% respectively, while HDL-C increased by 28.6% (all P<0.01). Hepatic histopathology showed remarkable reduction of lipid droplet accumulation in combination group compared to monotherapy. CONCLUSION: DLT significantly enhances systemic exposure of ATV in hyperlipidemic conditions by altering its pharmacokinetic profile. These findings suggest that when combining DLT with ATV in clinical practice, therapeutic efficacy and potential adverse reactions should be closely monitored, with particular attention to adjusting ATV dosing regimens to mitigate potential drug interaction risks.

Key words: atorvastatin, Dan-Lou tablets, pharmacokinetics, pharmacodynamics, UPLC-MS/MS

CLC Number:

R965.2

Ke ZHANG, Ziting LI, Fofo JIANG, Feng ZHAO, Yinling MA, Guoxun PANG. Effect of Dan-Lou tablets on the pharmacokinetics and pharmacodynamics of atorvastatin in high-fat diet-fed rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(3): 324-336.

Figures/Tables 17

References 39

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Compound	ATV	o-ATV	p-ATV	CMZ (IS)
Quantitative ion transition (m/z)	559.3→440.6	575.3→440.3	575.3→440.3	237.2→194.2
DP, V	130	91	91	110
CE, eV	30	33	33	13

Compound	ATV	o-ATV	p-ATV	CMZ (IS)
Quantitative ion transition (m/z)	559.3→440.6	575.3→440.3	575.3→440.3	237.2→194.2
DP, V	130	91	91	110
CE, eV	30	33	33	13

Group	Body weight (g)	TC (mmol/L)	TG (mmol/L)	HDL-C (mmol/L)	LDL-C (mmol/L)
Normal diet group	185.33±3.96	1.39±0.21	0.13±0.03	2.66±0.11	0.46±0.03
High-fat diet group	373.33±34.58^c	3.36±0.38^c	0.93±0.38^c	0.74±0.11^c	1.03±0.02^c

Group	Body weight (g)	TC (mmol/L)	TG (mmol/L)	HDL-C (mmol/L)	LDL-C (mmol/L)
Normal diet group	185.33±3.96	1.39±0.21	0.13±0.03	2.66±0.11	0.46±0.03
High-fat diet group	373.33±34.58^c	3.36±0.38^c	0.93±0.38^c	0.74±0.11^c	1.03±0.02^c

Compound	Concentration (ng/mL)	Intra-day			Inter-day
Compound	Concentration (ng/mL)	Determined concentrations (ng/mL)	Accuracy (%)	RSD (%)	Determined concentrations (ng/mL)	Accuracy (%)	RSD (%)
ATV	0.1	0.11±0.005	9.00	4.93	0.11±0.002	10.20	1.54
	0.5	0.46±0.03	?7.49	6.15	0.47±0.009	?6.16	2.00
	100	97.01±3.16	?2.99	3.26	98.24±1.73	?1.76	1.76
	250	249.71±4.82	?0.11	1.93	251.43±2.42	0.57	0.96
o-ATV	0.1	0.11±0.003	7.58	3.14	0.11±0.004	7.70	3.80
	0.5	0.46±0.009	?7.19	1.93	0.46±0.004	?7.74	0.84
	10	9.48±0.34	?10.50	7.52	10.54±0.09	?4.62	1.97
	24	24.55±0.84	2.27	3.41	24.63±0.12	2.61	0.47
p-ATV	0.1	0.11±0.006	12.08	5.23	0.11±0.008	12.72	7.07
	0.5	0.52±0.02	3.00	3.59	0.51±0.003	2.54	0.61
	10	10.42±0.13	4.22	1.20	10.42±1.39	4.19	0.13
	24	22.13±0.66	?7.80	3.00	22.00±0.11	?8.34	0.52