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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 -
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 -
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 -
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 -
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