ABSTRACT
With the initiation and development of the Human Microbiome Project (HMP) and the Project on Metagenomics of the Human Intestinal Tract (MetaHIT), the studies of the gut microbiota (GMB) have entered a fast lane and proved that GMB is associated with several diseases. Recent studies have confirmed that GMB affects and modulates pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, making it one of the potential focuses of precision medicine. This article presents an overview of the potential mechanisms of GMB affecting drug treatment and advances in the relevant studies, hoping to shed some new light on the precision therapeutic strategy.
ABSTRACT
OBJECTIVE: To evaluate the bioequivalence of cefdinir suspension and reference cefdinir capsule in Chinese healthy male subjects. METHODS: A single oral dose of 100 mg cefdinir suspension or cefdinir capsule was given to 24 subjects according to a 2-way crossover design. The plasma concentrations of cefdinir were determined by UPLC-MS/MS. The pharmacokinetic parameters were calculated and bioequivalence was compared by WinNonlin 6.3 program. RESULTS: The main pharmacokinetic parameters of cefdinir suspension and cefdinir capsule were as follow; ρmax were (1034.78±358.17), (969.71±297.38) ng·mL-1; tmax were (2.98±0.60), (3.44±0.70) h; AUC0-12 were (4911.24±1675.30), (4522.35±1600.13) ng·h·mL-1; AUC0-∞ were (5026.24±1735.32), (4680.69±1699.93) ng·h·mL-1;t1/2were (1.71±0.23), (1.79±0.39) h. The 90% confidential interval of ρmax, AUC0-12, AUC0-∞ of tested formulation were 95.6%-115.3%, 99.9%-117.2%, 99.0%-116.0%. CONCLUSION: The two formulations are bioequivalent.
ABSTRACT
This study established a population pharmacokinetics-pharmacodynamics model of clopidogrel in patients with acute coronary syndrome. Fifty-nine patients were enrolled. The plasma concentration of clopidogrel active metabolite and vasodilator stimulated phosphoprotein platelet reactivity index (VASP-PRI) were selected as the pharmacokinetics index and the pharmacodynamics index, respectively. The covariates including demographic characteristics, laboratory indexes, combined medication, complications and genetic polymorphisms of related enzymes were screened for their influence on the pharmacokinetic and pharmacodynamics parameters. Population pharmacokinetic and pharmacodynamics data analysis was performed using NONMEM software. The general linear model and the indirectly effect model-turnover model for pharmacokinetic and pharmacodynamic analysis were selected as the basic model, respectively. The population typical values of K12, CL/F, V/F, EC50, K(in), and E(max) were 0.259 h(-1), 179 L x h(-1), 632 L, 1.57 ng x mL(-1), 4.29 and 0.664, respectively. CYP2C19 was the covariate in the final pharmacokinetic model, and the model was to design a prior dosage regimen.