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Journal of Pharmaceutical and... Jun 2024Street cocaine is often mixed with various substances that intensify its harmful effects. This paper proposes a framework to identify attenuated total reflection Fourier...
Street cocaine is often mixed with various substances that intensify its harmful effects. This paper proposes a framework to identify attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) intervals that best predict the concentration of adulterants in cocaine samples. Wavelengths are ranked according to their relevance through ReliefF and mRMR feature selection approaches, and an iterative process removes less relevant wavelengths based on the ranking suggested by each approach. Gaussian Process (GP) regression models are constructed after each wavelength removal and the prediction performance is evaluated using RMSE. The subset balancing a low RMSE value and a small percentage of retained wavelengths is chosen. The proposed framework was validated using a dataset consisting of 345 samples of cocaine with different amounts of levamisole, caffeine, phenacetin, and lidocaine. Averaged over the four adulterants, the GP regression coupled with the mRMR retained 1.07 % of the 662 original wavelengths, outperforming PLS and SVR regarding prediction performance.
PubMed: 38889578
DOI: 10.1016/j.jpba.2024.116294 -
The Science of the Total Environment Jul 2024Phenacetin (PNCT) belongs to one of the earliest synthetic antipyretics. However, impact of PNCT on nitrifying microorganisms in wastewater treatment plants and its...
Phenacetin (PNCT) belongs to one of the earliest synthetic antipyretics. However, impact of PNCT on nitrifying microorganisms in wastewater treatment plants and its potential microbial mechanism was still unclear. In this study, PN could be initiated within six days by PNCT anaerobic soaking treatment (8 mg/L). In order to improve the stable performance of PN, 21 times of PNCT aerobic soaking treatment every three days was conducted and PN was stabilized for 191 days. After PN was damaged, ten times of PNCT aerobic soaking treatment every three days was conducted and PN was recovered after once soaking, maintained over 88 days. Ammonia oxidizing bacteria might change the dominant oligotype to gradually adjust to PNCT, and the increase of abundance and activity of Nitrosomonas promoted the initiation of PN. For nitrite-oxidizing bacteria (NOB), the increase of Candidatus Nitrotoga and Nitrospira destroyed PN, but PN could be recovered after once aerobic soaking illustrating NOB was not resistant to PNCT. KEGG and COG analysis suggested PNCT might disrupt rTCA cycle of Nitrospira, resulting in the decrease of relative abundance of Nitrospira. Moreover, PNCT did not lead to the sharp increase of absolute abundances of antibiotic resistance genes (ARGs), and the risk of ARGs transmission was negligible.
Topics: Nitrification; Waste Disposal, Fluid; Phenacetin; Wastewater; Drug Resistance, Microbial; Water Pollutants, Chemical; Bacteria
PubMed: 38744392
DOI: 10.1016/j.scitotenv.2024.173190 -
Biomedical Chromatography : BMC Jul 2024A simple and reliable HPLC-ultraviolet (HPLC-UV) method was developed and validated for the quantification of pritelivir in the samples of medium from the experiments...
A simple and reliable HPLC-ultraviolet (HPLC-UV) method was developed and validated for the quantification of pritelivir in the samples of medium from the experiments utilizing the ex vivo technique of dual perfusion of the human placental lobule. Phenacetin was used as an internal standard (IS) in our HPLC-UV method. Chromatographic separation of pritelivir and phenacetin was achieved on a Waters Symmetry C HPLC column (100 × 2.1 mm, 3.5 μm) at ambient temperature (22-25°C). The mobile phase was composed of 50% methanol in deionized water (v/v), the flow rate for isocratic elution was established at 0.25 mL/min, and the detection wavelength for pritelivir and IS was set at 254 nm. Pritelivir and IS were extracted with the protein precipitation method using methanol as a solvent. The calibration curve for pritelivir exhibited linearity (r > 0.99) within the concentration range from 0.155 to 6.62 μg/mL. Within- and between-day accuracy ranged from 97% to 110% with relative standard deviation (RSD) values not exceeding 10%. The extraction recovery of pritelivir and IS ranged from 89% to 91% with RSD not exceeding 7%. Pritelivir was stable under the storage and sample handling conditions. This validated HPLC-UV method was utilized to quantify pritelivir in the placental perfusion medium samples, and the resulting concentrations were authenticated with incurred sample reanalysis to confirm the reliability of the method.
Topics: Chromatography, High Pressure Liquid; Humans; Placenta; Female; Pregnancy; Reproducibility of Results; Linear Models; Limit of Detection; Spectrophotometry, Ultraviolet; Perfusion; Sulfonamides
PubMed: 38727008
DOI: 10.1002/bmc.5888 -
Heliyon May 2024Medication overuse headache (MOH) is a secondary headache disorder that leads to pronounced disability and decreased quality of life. Available therapeutic options for...
BACKGROUND
Medication overuse headache (MOH) is a secondary headache disorder that leads to pronounced disability and decreased quality of life. Available therapeutic options for MOH are limited, and many are only effective in a subset of individuals. Although the existing evidence is limited, acupuncture may be an effective treatment option for MOH.
CASE PRESENTATION
A 45-year-old Chinese woman presented to the Medical Acupuncture Department of Sanming Integrated Traditional Chinese and Western Medicine Hospital on April 11, 2022. Thirty-five years ago, she had episodic migraines. The frequency increased over time, however, and for the past 10 years she has had daily headaches. These headaches were characterized by daily persistent throbbing pain on the left side of the patient's head, accompanied by photophobia, phonophobia, neck stiffness, dizziness, and fatigue. Without painkillers, the patient rated her headache intensity as 9 out of 10 on a visual analog scale (0 = no pain, 10 = intolerable pain), and reported that the headaches lasted for up to 7 days or more. With painkillers, the headaches had a reduced intensity (5 of 10), but persisted. The patient had taken 1-3.5 compound aminopyrine phenacetin tablets daily for more than 5 years. Standard conservative therapy (patient education, medication withdrawal, and behavioral intervention) for MOH had failed to improve her symptoms. Before her visit, the patient had headache and engaged in short-term medication use on 30 days per month. The total monthly headache intensity score was 90. The patient's Migraine-Specific Quality of Life Questionnaire (MSQ) score was 33 points, her Hamilton Depression Scale (HAMD) score was 24 points, and her Hamilton Anxiety Scale (HAMA) score was 20 points.
RESULTS
After 48 acupuncture sessions over 24 weeks, the patient completely discontinued short-term analgesic use and the monthly number of headache days and headache intensity score were both reduced by 96.67 % (from 30 to 1 and 90 to 3, respectively), with no adverse effect. Compared with baseline, the MSQ, HAMD, and HAMA scores improved by 45, 17, and 16 points, respectively. At 12 months, the patient's condition remained stable and her MOH had not relapsed.
CONCLUSION
In the context of the current literature and the present case, electroacupuncture shows promise for the long-term relief of chronic migraine with MOH when other treatments fail.
PubMed: 38720738
DOI: 10.1016/j.heliyon.2024.e30417 -
Journal of Ethnopharmacology Aug 2024The combination of Aconitum carmichaelii Debx (Chuanwu, CW) and Pinellia ternata (Thunb.) Breit (Banxia, BX) forms an herbal pair within the eighteen incompatible...
ETHNOPHARMACOLOGICAL RELEVANCE
The combination of Aconitum carmichaelii Debx (Chuanwu, CW) and Pinellia ternata (Thunb.) Breit (Banxia, BX) forms an herbal pair within the eighteen incompatible medicaments (EIM), indicating that BX and CW are incompatible. However, the scientific understanding of this incompatibility mechanism, especially the corresponding drug-drug interaction (DDI), remains complex and unclear.
AIM OF THE STUDY
This study aims to explain the DDI and potential incompatibility mechanism between CW and BX based on pharmacokinetics and cocktail approach.
MATERIALS AND METHODS
Ultraperformance liquid chromatography-tandem mass spectrometry methods were established for pharmacokinetics and cocktail studies. To explore the DDI between BX and CW, in the pharmacokinetics study, 10 compounds were determined in rat plasma after administering CW and BX-CW herbal pair extracts. In the cocktail assay, the pharmacokinetic parameters of five probe substrates were utilized to assess the influence of BX on cytochrome P450 (CYP) isoenzyme (dapsone for CYP3A4, phenacetin for CYP1A2, dextromethorphan for CYP2D6, tolbutamide for CYP2C9, and omeprazole for CYP2C19). Finally, the DDI and incompatibility mechanism of CW and BX were integrated to explain the rationality of EIM theory.
RESULTS
BX not only enhances the absorption of aconitine and benzoylaconine but also accelerates the metabolism of mesaconitine, benzoylmesaconine, songorine, and fuziline. Moreover, BX affects the activity of CYP enzymes, which regulate the metabolism of toxic compounds.
CONCLUSIONS
BX altered the activity of CYP enzymes, consequently affecting the metabolism of toxic compounds from CW. This incompatibility mechanism may be related to the increased absorption of these toxic compounds in vivo.
Topics: Aconitum; Pinellia; Animals; Herb-Drug Interactions; Rats, Sprague-Dawley; Male; Rats; Cytochrome P-450 Enzyme System; Tandem Mass Spectrometry; Plant Extracts; Drugs, Chinese Herbal; Drug Interactions
PubMed: 38636577
DOI: 10.1016/j.jep.2024.118212 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Apr 2024The pain-relieving effect and safety of compound aminopyrine phenacetin tablets, tramcontin (tramadol hydrochloride sustained-release tablets) and dolantin in the early... (Comparative Study)
Comparative Study
OBJECTIVE
The pain-relieving effect and safety of compound aminopyrine phenacetin tablets, tramcontin (tramadol hydrochloride sustained-release tablets) and dolantin in the early stage of autologous tendon reconstruction of the anterior cruciate ligament (ACL) of the knee joint were compared.
METHODS
Retrospective analysis of postoperative pain and drug analgesia in 45 patients performed by the same group from November 2018 to February 2019. The random area group design was divided into two groups according to whether ACL rupture was combined with meniscal injury, group A was 24 patients with ACL reconstruction of knee joint and group B was 21 patients with ACL fracture combined with meniscus injury. The two groups were divided into three subgroups respectively according to the actual treatment of postoperative analgesic drugs received by the patients, including 4 cases of compound aminopyrine phenacetin tablets, 11 cases of oral tramcontin, 9 cases of intramuscular dolantin combined with phenergan in group A; 3 cases of compound aminopyrine phenacetin tablets, 10 cases of oral tramcontin, and 8 cases of intramuscular dolantin combined with phenergan in group B. When the early postoperative patients complain about pain and actively ask for analgesia. When the patients complained about pain after the operation and actively asked for analgesia, they were randomly given painkillers, tramcontin or dolantin combined with phenergan to relieve pain. Pain visual analogue scale (VAS) was used to evaluate pain relief and observe the occurrence of adverse reactions.
RESULTS
There were no significant dif-ferences in gender, age, body mass index, and time of hospital stay between the two groups of patients ( > 0.05). In the patients who used tramcontin and dolantin combined with phenergan to relieve pain judging by VAS score before and 1 h after taking the drug, it was found that the pain situation of the patient was significantly relieved, and the difference before and after taking the drug had statistical significance ( < 0.05). Pairwise comparisons of the three drugs applied in the two groups showed significantly greater pain relief in the dolantin combined with phenergan group than in the remaining two drugs. There was no significant difference ( > 0.05). Dolantin was prone to nausea and vomiting, but the application of phenergan was also used to reduce side effects. In terms of adverse reactions, only 1 case of nausea occurred in the tramcontin group for simple ACL reconstruction, and none of the patients in the other groups showed serious complications and allergic reactions.
CONCLUSION
Whether in cruciate ligament reconstruction alone or combined with meniscus molding or suture, compound aminopyrine phenacetin tablets, tramcontin, dolantin combined with phenergan can effectively relieve pain. Among the three drugs, dolantin caused the largest pain relief. At the same time, the combination of phenergan effectively reduced the adverse reactions, such as vomiting and nausea, and increased the drug safety.
Topics: Humans; Aminopyrine; Analgesics; Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Knee Joint; Meperidine; Nausea; Pain, Postoperative; Phenacetin; Promethazine; Retrospective Studies; Treatment Outcome; Vomiting
PubMed: 38595247
DOI: 10.19723/j.issn.1671-167X.2024.02.014 -
Materials (Basel, Switzerland) Jan 2024Acetaminophen (CHNO, also called paracetamol) is an active metabolite of phenacetin with antipyretic and analgesic effects and has been extensively used as a painkiller....
Acetaminophen (CHNO, also called paracetamol) is an active metabolite of phenacetin with antipyretic and analgesic effects and has been extensively used as a painkiller. Currently, the problem of pharmaceuticals in water and sewage is common, especially in highly urbanized countries. Laboratory-scale experiments were carried out using an adsorbent-granulated activated carbon (WD-extra)-to remove acetaminophen (ACT) from water. The initial concentration of acetaminophen was 20 mg ACT/dm. The adsorption kinetics, influence of the pH on adsorption and dose of the used adsorbent were determined under batch conditions. The adsorption of ACT on activated carbon was more efficient when the water solution was acidic (at pH 2, it was the most effective). The highest percentage of removal (99%) was obtained for the WD-extra dose of 10.0 g/dm. The time taken to establish the dynamic equilibrium of the system was 60 min. The effectiveness of adsorption was determined based on the Freundlich and Langmuir adsorption isotherms. It was found that WD-extra activated carbon effectively removed ACT from water solutions.
PubMed: 38255599
DOI: 10.3390/ma17020431 -
Chemico-biological Interactions Jan 2024Ciprofol is a novel intravenous anesthetic agent. Its major glucuronide metabolite, M4, is found in plasma and urine. However, the specific isoforms of...
Ciprofol is a novel intravenous anesthetic agent. Its major glucuronide metabolite, M4, is found in plasma and urine. However, the specific isoforms of UDP-glucuronosyltransferases (UGTs) that metabolize ciprofol to M4 remain unknown. This study systematically characterized UGTs that contribute to the formation of M4 using human liver microsomes (HLM), human intestinal microsomes (HIM), and human recombinant UGTs. The inhibitory potential of ciprofol and M4 against major human UGTs and cytochrome P450 enzymes (P450s) was also explored. In vitro-in vivo extrapolation (IVIVE) and physiologically-based pharmacokinetic (PBPK) simulations were performed to predict potential in vivo drug-drug interactions (DDIs) caused by ciprofol. Glucuronidation of ciprofol followed Michaelis-Menten kinetics in both HLM and HIM with apparent K values of 345 and 412 μM, V values of 2214 and 444 nmol min·mg protein, respectively. The in vitro intrinsic clearances (CL = V/K) for ciprofol glucuronidation by HLM and HIM were 6.4 and 1.1 μL min·mg protein, respectively. Human recombinant UGT studies revealed that UGT1A9 is the predominant isoform mediating M4 formation, followed by UGT1A7, with UGT1A8 playing a minor role. Ciprofol competitively inhibited CYP1A2 (K = 12 μM) and CYP2B6 (K = 4.7 μM), and noncompetitively inhibited CYP2C19 (K = 29 μM). No time-dependent inhibition by ciprofol was noted for CYP1A2, CYP2B6, or CYP2C19. In contrast, M4 showed limited or no inhibitory effects against selected P450s. Neither ciprofol nor M4 inhibited UGTs significantly. Initial IVIVE suggested potential ciprofol-mediated inhibition of CYP1A2, CYP2B6, and CYP2C19 inhibition in vivo. However, PBPK simulations showed no significant effect on phenacetin, bupropion, and S-mephenytoin exposure or peak plasma concentration. Our findings are pertinent for future DDI studies of ciprofol as either a perpetrator or victim drug.
Topics: Humans; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2C19; Microsomes, Liver; Glucuronosyltransferase; Drug Interactions; Kinetics
PubMed: 37993078
DOI: 10.1016/j.cbi.2023.110811 -
IUCrData Jul 2023The title compound, CHNO, crystallizes with ' = 2 in space group 2 with the two independent mol-ecules having almost the same conformation, differing mostly at the end...
The title compound, CHNO, crystallizes with ' = 2 in space group 2 with the two independent mol-ecules having almost the same conformation, differing mostly at the end of the butanamide chain. A local inversion center near 1/8, 3/4, relates the two mol-ecules, as is common for structures in this space group with ' = 2. The mol-ecule crystallizes as the keto tautomer, and the β-diketone moieties are twisted out of planarity, with O-C⋯C-O pseudo torsion angles of -74.4 (5) and -83.9 (5)°. The N-H group of each independent mol-ecule donates an inter-molecular hydrogen bond to an amide carbonyl oxygen atom by positive or negative translations along the axis, thus forming anti-parallel chains propagating in the [010] direction.
PubMed: 37937129
DOI: 10.1107/S2414314623005655 -
Molecules (Basel, Switzerland) Oct 2023Lekethromycin (LKMS) is a synthetic macrolide compound derivative intended for use as a veterinary medicine. Since there have been no in vitro studies evaluating its...
Lekethromycin (LKMS) is a synthetic macrolide compound derivative intended for use as a veterinary medicine. Since there have been no in vitro studies evaluating its potential for drug-drug interactions related to cytochrome P450 (CYP450) enzymes, the effect of the inhibitory mechanisms of LKMS on CYP450 enzymes is still unclear. Thus, this study aimed to evaluate the inhibitory effects of LKMS on dog CYP450 enzymes. A cocktail approach using ultra-performance liquid chromatography-tandem mass spectrometry was conducted to investigate the inhibitory effect of LKMS on canine CYP450 enzymes. Typical probe substrates of phenacetin, coumarin, bupropion, tolbutamide, dextromethorphan, chlorzoxazone, and testosterone were used for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4, respectively. This study showed that LKMS might not be a time-dependent inhibitor. LKMS inhibited CYP2A6, CYP2B6, and CYP2D6 via mixed inhibition. LKMS exhibited mixed-type inhibition against the activity of CYP2A6 with an inhibition constant (K) value of 135.6 μΜ. LKMS inhibited CYP2B6 in a mixed way, with K values of 59.44 μM. A phenotyping study based on an inhibition assay indicated that CYP2D6 contributes to the biotransformation of LKMS. A mixed inhibition of CYP2D6 with K values of 64.87 μM was also observed. Given that this study was performed in vitro, further in vivo studies should be conducted to identify the interaction between LKMS and canine CYP450 enzymes to provide data support for the clinical application of LKMS and the avoidance of adverse interactions between other drugs.
Topics: Dogs; Animals; Tandem Mass Spectrometry; Chromatography, Liquid; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2D6; Microsomes, Liver; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Liver
PubMed: 37894672
DOI: 10.3390/molecules28207193