title: Pharmacokinetic-Pharmacodynamic Modeling to Study the Antipyretic Effect of Qingkailing Injection on Pyrexia Model Rats.
abstract: 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.
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, South of Wangjing Middle Ring Road, Chaoyang District, Beijing 100102, China. zzxzxz@163.com.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, South of Wangjing Middle Ring Road, Chaoyang District, Beijing 100102, China. lingling19900220@126.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Qin
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, South of Wangjing Middle Ring Road, Chaoyang District, Beijing 100102, China. penglong0829@163.com.
authors.forename: Long
authors.initials: L
authors.lastname: Peng
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, South of Wangjing Middle Ring Road, Chaoyang District, Beijing 100102, China. janezh1987@sina.com.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, South of Wangjing Middle Ring Road, Chaoyang District, Beijing 100102, China. shadow152324@126.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, South of Wangjing Middle Ring Road, Chaoyang District, Beijing 100102, China. bucm1989@163.com.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road, Chaoyang District, Beijing 100029, China. syltwc2005@163.com.
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Song
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, South of Wangjing Middle Ring Road, Chaoyang District, Beijing 100102, China. gaoxiaoyan0913@sina.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D058633:Antipyretics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005334:Fever / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D005419:Flavonoids / Q000493:pharmacokinetics; D039823:Iridoids / Q000493:pharmacokinetics; D008297:Male; D008516:Medicine, Chinese Traditional; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058633:Antipyretics; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D039823:Iridoids; C504928:Qingkailing; C000594495:an-gong-niu-huang wan; C007835:geniposide; C038044:baicalin
keywords: PK marker; Qingkailing injection; antipyretic effect; pharmacokinetic-pharmacodynamic model