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Molecules 2016, 21(3), 317; doi:10.3390/molecules21030317

Pharmacokinetic-Pharmacodynamic Modeling to Study the Antipyretic Effect of Qingkailing Injection on Pyrexia Model Rats

School of Chinese Pharmacy, Beijing University of Chinese Medicine, South of Wangjing Middle Ring Road, Chaoyang District, Beijing 100102, China
Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road, Chaoyang District, Beijing 100029, China
These authors contribute equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 4 January 2016 / Revised: 26 February 2016 / Accepted: 26 February 2016 / Published: 7 March 2016
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [13344 KB, uploaded 7 March 2016]   |  


Qingkailing injection (QKLI) is a modern Chinese medicine preparation derived from a well-known classical formulation, An-Gong-Niu-Huang Wan. Although the clinical efficacy of QKLI has been well defined, its severe adverse drug reactions (ADRs) were extensively increased. Through thorough attempts to reduce ADR rates, it was realized that the effect-based rational use plays the key role in clinical practices. Hence, the pharmacokinetic-pharmacodynamic (PK-PD) model was introduced in the present study, aiming to link the pharmacokinetic profiles with the therapeutic outcomes of QKLI, and subsequently to provide valuable guidelines for the rational use of QKLI in clinical settings. The PK properties of the six dominant ingredients in QKLI were compared between the normal treated group (NTG) and the pyrexia model group (MTG). Rectal temperatures were measured in parallel with blood sampling for NTG, MTG, model control group (MCG), and normal control group (NCG). Baicalin and geniposide exhibited appropriate PK parameters, and were selected as the PK markers to map the antipyretic effect of QKLI. Then, a PK-PD model was constructed upon the bacalin and geniposide plasma concentrations vs. the rectal temperature variation values, by a two-compartment PK model with a Sigmoid Emax PD model to explain the time delay between the drug plasma concentration of PK markers and the antipyretic effect after a single dose administration of QKLI. The findings obtained would provide fundamental information to propose a more reasonable dosage regimen and improve the level of individualized drug therapy in clinical settings. View Full-Text
Keywords: pharmacokinetic-pharmacodynamic model; antipyretic effect; Qingkailing injection; PK marker pharmacokinetic-pharmacodynamic model; antipyretic effect; Qingkailing injection; PK marker

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Zhang, Z.; Qin, L.; Peng, L.; Zhang, Q.; Wang, Q.; Lu, Z.; Song, Y.; Gao, X. Pharmacokinetic-Pharmacodynamic Modeling to Study the Antipyretic Effect of Qingkailing Injection on Pyrexia Model Rats. Molecules 2016, 21, 317.

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