-
Evidence-based Complementary and... 2019Naoxintong capsule (NXT), a prescribed Chinese medicine, has been used clinically for more than 20 years and is widely received by patients. We determined five probe...
Naoxintong capsule (NXT), a prescribed Chinese medicine, has been used clinically for more than 20 years and is widely received by patients. We determined five probe drugs, namely, omeprazole (CYP2C19), midazolam (CYP3A4), phenacetin (CYP1A2), tolbutamide (CYP2C9), and dextromethorphan (CYP2D6) to study the potential influences of NXT on the activities of CYP enzymes and assessed the pharmacokinetics effect of NXT on metoprolol tartrate in rat plasma. The study showed that AUC and AUC of midazolam (CYP3A4) in NXT coadministration group (283.7 ± 65.2 h·ng·mL and 292.0 ± 75.1 h·ng·mL in group B; 295.7 ± 62.7 h·ng·mL and 299.5 ± 60.0 h·ng·mL in group C) were significantly decreased as compared to another group (416.8 ± 82.3 h·ng·mL and 424.9 ± 77.9 h·ng·mL in group A), while that of dextromethorphan (CYP2D6) showed an opposite tendency (540.7 ± 119.7 h·ng·mL and 595.3 ± 122.2 h·ng·mL in group A, 760.6 ± 184.9 h·ng·mL and 788.7 ± 211.0 h·ng·mL in group B, and 734.3 ± 118.5 h·ng·mL and 757.2 ± 105.4 h·ng·mL in group C). Moreover, NXT preadministration can enhance the metabolism of metoprolol tartrate and reduce the metabolism of O-demethylmetoprolol. The results indicated that NXT had potential effects in inducing CYP3A4 and inhibiting CYP2D6 in the metabolism of metoprolol tartrate. It suggests that patients who coadministered NXT and metoprolol tartrate should be advised of potential herb-drug interactions (HDIs) to reduce therapeutic failure or accelerated toxicity of conventional drug treatment.
PubMed: 31662775
DOI: 10.1155/2019/5242605 -
ACS Omega Oct 2019A new method of data interpretation based on classical nucleation theory is proposed in this work to elucidate the influence of solvents on the pre-exponential...
A new method of data interpretation based on classical nucleation theory is proposed in this work to elucidate the influence of solvents on the pre-exponential nucleation factor and interfacial energy using the induction time data for three crystallization systems, including isonicotinamide, lovastatin, and phenacetin. In this method, the pre-exponential nucleation factor is replaced by the intrinsic nucleation factor multiplied by temperature and divided by solution viscosity. The proposed method is applied to study the nucleation kinetics of isonicotinamide, lovastatin, and phenacetin among various solvents using the induction time data measured in this work. The results indicate that the intrinsic nucleation factor increases linearly with increasing square root of interfacial energy in various solvents for each system.
PubMed: 31656908
DOI: 10.1021/acsomega.9b02102 -
Biological & Pharmaceutical Bulletin Jan 2020To improve the efficiency of drug-discovery research on pyrrole-imidazole polyamides (PIs), a more rapid method for quantitative and qualitative measurement of PI in rat...
To improve the efficiency of drug-discovery research on pyrrole-imidazole polyamides (PIs), a more rapid method for quantitative and qualitative measurement of PI in rat plasma samples was developed here using ultra-fast liquid chromatography-ultraviolet spectrometry (UFLC-UV) in order to shorten the measurement time. A measurement method of PIs by HPLC developed until now takes 45 min for one sample measurement. This method was inefficient to investigate extraction conditions from biological samples and measurement of animal experimental samples. In the developed method of this study, PI and phenacetin (internal standard, IS) were separated with an ACQUITY UPLC HSS T3 (1.8 µm, 2.1 × 50 mm; Nihon Waters K.K., Japan) column using a mobile phase of 0.1% acetic acid (mobile phase A) and acetonitrile (mobile phase B) at a flow rate of 0.3 mL/min with a linear gradient. The detection wavelength was 310 nm. The calibration curve was linear in the range of 0.225-4.5 µg/mL (correlation coefficients ≥0.9995, n = 5). The intra- and inter-day accuracies were in the range of -6.04 to 12.2%, and the precision was less than 2.99%. The measurement time of this method (7 min per injection) was markedly shortened to about one-sixth of the previous measurement time (45 min per injection). This is the first report describing the quantitative and qualitative measurement of PI in plasma using UFLC-UV. The present method will be very useful for the drug-discovery research of PIs.
Topics: Animals; Calibration; Chromatography, High Pressure Liquid; Imidazoles; Male; Molecular Structure; Pyrroles; Rats, Sprague-Dawley; Reference Standards; Reproducibility of Results; Spectrophotometry, Ultraviolet
PubMed: 31645526
DOI: 10.1248/bpb.b19-00644 -
Molecules (Basel, Switzerland) Sep 2019Cytochromes P450 are major metabolic enzymes involved in the biotransformation of xenobiotics. The majority of xenobiotics are metabolized in the liver, in which the...
Cytochromes P450 are major metabolic enzymes involved in the biotransformation of xenobiotics. The majority of xenobiotics are metabolized in the liver, in which the highest levels of cytochromes P450 are expressed. Flavonoids are natural compounds to which humans are exposed through everyday diet. In the previous study, selected flavonoid aglycones showed inhibition of CYP3A4 enzyme. Thus, the objective of this study was to determine if these flavonoids inhibit metabolic activity of CYP1A2, CYP2A6, CYP2C8, and CYP2D6 enzymes. For this purpose, the -deethylation reaction of phenacetin was used for monitoring CYP1A2 enzyme activity, coumarin 7-hydroxylation for CYP2A6 enzyme activity, 6-α-hydroxylation of paclitaxel for CYP2C8 enzyme activity, and dextromethorphan -demethylation for CYP2D6 enzyme activity. The generated metabolites were monitored by high-performance liquid chromatography coupled with diode array detection. Hesperetin, pinocembrin, chrysin, isorhamnetin, and morin inhibited CYP1A2 activity; apigenin, tangeretin, galangin, and isorhamnetin inhibited CYP2A6 activity; and chrysin, chrysin-dimethylether, and galangin inhibited CYP2C8. None of the analyzed flavonoids showed inhibition of CYP2D6. The flavonoids in this study were mainly reversible inhibitors of CYP1A2 and CYP2A6, while the inhibition of CYP2C8 was of mixed type (reversible and irreversible). The most prominent reversible inhibitor of CYP1A2 was chrysin, and this was confirmed by the docking study.
Topics: Cytochrome P-450 Enzyme System; Flavonoids; Humans; Molecular Docking Simulation; Substrate Specificity
PubMed: 31480528
DOI: 10.3390/molecules24173174 -
Trends in Psychiatry and Psychotherapy Jul 2019Brazil is the world's biggest consumer of crack cocaine, and dependence is a major public health issue. This is the first study to investigate the prevalence of...
INTRODUCTION
Brazil is the world's biggest consumer of crack cocaine, and dependence is a major public health issue. This is the first study to investigate the prevalence of potentially harmful adulterants present in hair samples from Brazilian patients with crack cocaine dependence.
METHOD
We evaluated adulterants in hair samples extracted by convenience from 100 patients admitted at the 48 hour-observation unit of Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), Brazil's largest center for addiction treatment. A cross-sectional analysis was performed with the data obtained.
RESULTS
Adulterants were found in 97% of the analyzed hair samples. The most prevalent adulterant was lidocaine (92%), followed by phenacetin (69%) and levamisole (31%).
CONCLUSION
Adulterants were widely prevalent in hair samples from crack users treated at CRATOD: at least one adulterant was present in virtually all the hair samples collected. This points to a need to monitor adverse effects in the clinical setting in order to provide this high-risk group of patients with prompt and effective care related to the acute and chronic complications associated with these adulterants.
Topics: Adolescent; Adult; Brazil; Cocaine-Related Disorders; Crack Cocaine; Drug Contamination; Female; Hair; Humans; Levamisole; Lidocaine; Male; Phenacetin; Young Adult
PubMed: 31314858
DOI: 10.1590/2237-6089-2017-0143