The effect of malaria-induced alteration of metabolism on piperaquine disposition in Plasmodium yoelii infected mice and predicted in malaria patients.

Objectives: Malaria-induced alteration of physiological parameters and pharmacokinetic properties of antimalarial drugs may be clinically relevant. Whether and how malaria alters the disposition of piperaquine (PQ) was investigated in this study.

Methods: The effect of malaria on drug metabolism-related enzymes and PQ pharmacokinetic profiles was studied in Plasmodium yoelii-infected mice in vitro/in vivo.

Vasoprotective Effects of Hyperoside against Cerebral Ischemia/Reperfusion Injury in Rats: Activation of Large-Conductance Ca-Activated K Channels.

Hyperoside (Hyp), a kind of Chinese herbal medicine, exerts multiple therapeutic effects on many diseases. However, the role and mechanisms of Hyp in vascular pathophysiology in ischemic stroke need to be further established. The study aimed to investigate the role of (large-conductance Ca-activated K) BK channels on the vasoprotection of Hyp against cerebral ischemia and reperfusion (I/R) injury in rats.

The Effect of Retroconversion Metabolism of -oxide Metabolites by Intestinal Microflora on Piperaquine Elimination in Mice, as well as in Humans Predicted Using a PBPK Model.

Background: Piperaquine (PQ) and its pharmacologically active metabolite PQ -oxide (PM1) can be metabolically interconverted via hepatic cytochrome P450 and FMO enzymes.

Objectives: The reductive metabolism of PM1 and its further -oxidation metabolite (PM2) by intestinal microflora was evaluated, and its role in PQ elimination was also investigated.

Methods: The hepatic and microbial reduction metabolism of PM1 and PM2 was studied .

Case Report: Aumolertinib as Neoadjuvant Therapy for Patients With Unresectable Stage III Non-Small Cell Lung Cancer With Activated EGFR Mutation: Case Series.

Background: There is no standard treatment for stage III lung cancer due to its low surgical resection rate, and improving PFS and survival of patients with III NSCLC has become an urgent challenge in clinical treatment. For EGFR mutation-positive patients, targeted therapy has the remarkable feature of high efficiency and low toxicity compared with first-line standard chemotherapy, and targeted neoadjuvant therapy needs to be further explored.

Method: We report 3 diagnosed cases of locally advanced unresectable NSCLC with EGFR-sensitive mutations who first received 1-2 cycles of preoperative chemotherapy neoadjuvant therapy and were treated with 110 mg daily of 3rd-generation EGFR-TKI aumolertinib instead because of poor efficacy or safety intolerance.

No Effect of PXR (8055C>T) Polymorphism on the Pharmacokinetic Profiles of Piperaquine in Healthy Chinese Subjects.

Background: Significant inter-subject variability in pharmacokinetics and clinical outcomes has been observed for the antimalarial agent piperaquine (PQ). PQ is metabolized by CYP3A4, mainly regulated by the pregnane X receptor (PXR). CYP3A4(*1B) polymorphism did not affect PQ clearance.

Metabolism is not a Major Contributor to the Toxicity of Piperaquine, a Long-acting Antimalarial Agent in Artemisinin-based Combination Therapy.

Background: Hepatocellular damage has been reported for the antimalarial piperaquine (PQ) in the clinic after cumulative doses.

Objectives: The role of metabolism in PQ toxicity was evaluated, and the mechanism mediating PQ hepatotoxicity was investigated.

Methods: The toxicity of PQ and its major metabolite (PQ N-oxide; M1) in mice was evaluated in terms of serum biochemical parameters.

Metabolic Retroversion of Piperaquine (PQ) via Hepatic Cytochrome P450-Mediated -Oxidation and Reduction: Not an Important Contributor to the Prolonged Elimination of PQ.

As a partner antimalarial with an extremely long elimination half-life (∼30 days), piperaquine (PQ) is mainly metabolized into a pharmacologically active -oxide metabolite [piperaquine -oxide (PN1)] in humans. In the present work, the metabolic retroversion of PQ and PN1, potentially associated with decreased clearance of PQ, was studied. The results showed that interconversion existed for PQ and its metabolite PN1.

Rapid Profiling of the Marker Components in Artemisia annua L. and their Metabolites in Rats Using an Improved Liquid Chromatography-tandem Highresolution Mass Spectrometry-based Technology.

Background: As parasite resistance to the main artemisinin drugs has emerged in Southern Asia, the traditional herb Artemisia annua L. (AAL) from which artemisinin (QHS) isolated was found to overcome resistance to QHS. However the component and metabolite profiles of AAL remain unclear.

The Effect of Gastric pH on the Pharmacokinetics-pharmacodynamics of Naphthoquine in Rodents, as well as in Human Predicted Using a PBPK Model.

Background: Fixed-dose combination of artemisinin and naphthoquine (NQ) is a new artemisinin- based combination therapy for the treatment of uncomplicated Plasmodium falciparum. NQ absorption has been reported to be affected by food in humans.

Objectives: The effect of gastric pH on NQ pharmacokinetics and antiplasmodial activity was investigated.

Simultaneous determination of five alkaloids from Rauvolfia vomitoria in rat plasma by LC-MS/MS: Application to a comparative pharmacokinetic study in normal and type 2 diabetic rats.

Rauvolfia vomitoria is widely distributed in the tropical regions of Africa and Asia, and has been used in traditional folk medicine in China. Indole alkaloids were found to be major bioactive components, while the effects of diabetes mellitus on the pharmacokinetic parameters of the components have not been reflected in vivo. In this study, an efficient and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of five ingredients of R.

The gender-related variability in the pharmacokinetics and antiplasmodial activity of naphthoquine in rodents.

Background: Naphthoquine (NQ) is a suitable partner anti-malarial for the artemisinin-based combination therapy (ACT), which is recommended to be taken orally as a single-dose regimen. The metabolism of NQ was mainly mediated by CYP2D6, which is well-known to show gender-specific differences in its expression. In spite of its clinical use, there is limited information on the pharmacokinetics of NQ, and no data are available for females.