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 E max 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.

Network Pharmacology‐Based Approach to Revealing Biological Mechanisms of Qingkailing Injection against IschemicStroke: Focusing on Blood‐Brain Barrier

“…Pinoresinol [ 60 ] and tryptanthrin [ 61 ] induced a neuroinflammatory response and oxidative stress following brain ischemia. Unlike our results, baicalin, geniposide, cholic acid, and hyodeoxycholic acid were documented as the four important compounds of QKL [ 62 ]. Further studies should evaluate potential anti-ischemic stroke effect of these active compounds identified by our network pharmacological approach.…”

Qing-Kai-Ling Injection Induces Immediate Hypersensitivity Reaction via the Activation of Anaphylatoxin C3

“…brings increasing rapidly cases of adverse drug reaction (ADR) (Li et al, 2010), and an alarm over QKLI-caused potential risks in patients was released by the Chinese National Center for Adverse Drug Reaction Monitoring in June 2008and April 2009, respectively (National Center for ADR Monitoring, 2008National Center for ADR Monitoring, 2009). In fact, QKLI is the second leading cause of ADRs induced by traditional Chinese medicine injections (Zhang et al, 2016).…”

Divergence and Convergence of Cerebral Ischemia Pathways Profile Deciphers Differential Pure Additive and Synergistic Mechanisms

“…In previous studies, combination of BA and JA (BJ) have been demonstrated to exert an additive effect, while combination of JA and UA (JU) acted synergistically in treating cerebral ischemia (Chen et al, 2013;Yu et al, 2016;Zhang et al, 2016;. The monocomponents of BA, JA, or UA was proved to have multiple pharmacological functions, such as antiinflammatory (Chen et al, 2018;Kang et al, 2018;Ko et al, 2019), antioxidant (Srinivas, 2010), neuroprotective (Wu et al, 2018;, antiplatelet (Lee et al, 2015), and protein response (Vang et al, 2014).…”

“…The monocomponents of BA, JA, or UA was proved to have multiple pharmacological functions, such as antiinflammatory (Chen et al, 2018;Kang et al, 2018;Ko et al, 2019), antioxidant (Srinivas, 2010), neuroprotective (Wu et al, 2018;, antiplatelet (Lee et al, 2015), and protein response (Vang et al, 2014). Both of BA and JA regulated PI3K-Akt-PKB-BAD-CREB-PCREB pathway (Zhang et al, 2016); both of JA and UA acted on corticotropin releasing hormone signaling pathway (Chen et al, 2013). The combination therapy of JU exhibited both similarity and diversity in terms of signaling pathways.…”