scholarly journals Pharmacokinetics of Mephedrone Enantiomers in Whole Blood after a Controlled Intranasal Administration to Healthy Human Volunteers

2020 ◽  
Vol 14 (1) ◽  
pp. 5
Author(s):  
Joanna Czerwinska ◽  
Mark C. Parkin ◽  
Agostino Cilibrizzi ◽  
Claire George ◽  
Andrew T. Kicman ◽  
...  
Keyword(s):  
Whole Blood ◽  
Intranasal Administration ◽  
Chiral Recognition ◽  
Area Under The Curve ◽  
Healthy Human ◽  
Enantiomeric Ratio ◽  
Human Volunteers ◽  
Liquid Chromatography Tandem Mass ◽  
Neurological Effects ◽  
Enantioselective Pharmacokinetics

Mephedrone, which is one of the most popular synthetic cathinones, has one chiral centre and thus exists as two enantiomers: R-(+)-mephedrone and S-(−)-mephedrone. There are some preliminary data suggesting that the enantiomers of mephedrone may display enantioselective pharmacokinetics and exhibit different neurological effects. In this study, enantiomers of mephedrone were resolved via chromatographic chiral recognition and the absolute configuration was unambiguously determined by a combination of elution order and chiroptical analysis (i.e., circular dichroism). A chiral liquid chromatography tandem mass spectrometry method was fully validated and was applied to the analysis of whole blood samples collected from a controlled intranasal administration of racemic mephedrone hydrochloride to healthy male volunteers. Both enantiomers showed similar kinetics, however, R-(+)-mephedrone had a greater mean Cmax of 48.5 ± 11.9 ng/mL and a longer mean half-life of 1.92 ± 0.27 h compared with 44.6 ± 11.8 ng/mL and 1.63 ± 0.23 h for S-(−)-mephedrone, respectively. Moreover, R-(+)-mephedrone had a lower mean clearance and roughly 1.3 times greater mean area under the curve than S-(−)-mephedrone. Significant changes in the enantiomeric ratio over time were observed, which suggest that the analytes exhibit enantioselective pharmacokinetics. Even though the clinical significance of this finding is not yet fully understood, the study confirms that the chiral nature, and consequently the enantiomeric purity of mephedrone, can be a crucial consideration when interpreting toxicological results.

Pharmacokinetics of Mephedrone and Its Metabolites in Whole Blood and Plasma after Controlled Intranasal Administration to Healthy Human Volunteers

2020 ◽  
Author(s):  
Joanna Czerwinska ◽  
Mark C Parkin ◽  
Claire George ◽  
Andrew T Kicman ◽  
Paul I Dargan ◽  
...  
Keyword(s):  
Whole Blood ◽  
Intranasal Administration ◽  
Plasma Samples ◽  
Healthy Human ◽  
Rapid Absorption ◽  
Plasma Distribution ◽  
Human Volunteers ◽  
Liquid Chromatography Tandem Mass ◽  
Synthetic Cathinone ◽  
First Time

Abstract Mephedrone is a popular synthetic cathinone, known for its psychostimulant effects. At present, there is no data available on the pharmacokinetics of mephedrone and its metabolites in concurrently collected whole blood and plasma samples after a controlled intranasal administration to healthy volunteers. In this study, six healthy male volunteers nasally insufflated 100 mg of pure mephedrone hydrochloride (Day 1). Whole blood and plasma samples were collected at different time points after the administration and were analyzed for the presence of mephedrone and its metabolites, dihydro-mephedrone (DHM), nor-mephedrone (NOR), hydroxytolyl-mephedrone (HYDROXY), 4-carboxy-mephedrone (4-CARBOXY) and dihydro-nor-mephedrone (DHNM), by validated liquid chromatography–tandem mass spectrometry methods. All analytes were detected in whole blood and plasma for 6 h post administration, with mephedrone and NOR also being detectable on Day 2 in some participants. 4-CARBOXY, followed by NOR, was the most abundant metabolite in both matrices. Compared to other psychostimulants, mephedrone showed rapid absorption (mean Tmax of 52.5 ± 20.7 min in plasma and 55.0 ± 18.2 min in whole blood) and elimination (mean t1/2 of 1.98 ± 0.30 h in plasma and 2.12 ± 0.33 h in whole blood). In addition, statistical analysis showed that median whole blood to plasma distribution ratios, reported here for the first time, were statistically different from 1 (unity) for mephedrone (median: 1.11), DHM (median: 1.30) and NOR (median: 0.765). It is hoped that the study will aid forensic and clinical toxicologists in detection, identification and interpretation of cases associated with mephedrone use.

Determination of Factors Affecting Glutamate Concentrations in the Whole Blood of Healthy Human Volunteers

2011 ◽  
Vol 23 (1) ◽  
pp. 45-49 ◽  
Author(s):  
Alexander Zlotnik ◽  
Sharon Ohayon ◽  
Benjamin F. Gruenbaum ◽  
Shaun E. Gruenbaum ◽  
Boaz Mohar ◽  
...  
Keyword(s):  
Whole Blood ◽  
Healthy Human ◽  
Factors Affecting ◽  
Human Volunteers

scholarly journals A Liquid Chromatography-Tandem Mass Spectrometry Method for Evaluation of Two Brands of Enalapril 20 mg Tablets in Healthy Human Volunteers

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Wael Abu Dayyih ◽  
Mohammed Hamad ◽  
Ahmad Abu Awwad ◽  
Eyad Mallah ◽  
Zainab Zakarya ◽  
...  
Keyword(s):  
Enzyme Inhibitor ◽  
Internal Standard ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Chronic Heart Disease ◽  
Chromatography Tandem Mass Spectrometry ◽  
Human Volunteers ◽  
Treatment Of Hypertension ◽  
Liquid Chromatography Tandem Mass ◽  
Enalapril And Enalaprilat

Enalapril is an angiotensin-converting enzyme inhibitor used for treatment of hypertension and chronic heart disease. Enalaprilat is its active metabolite responsible for the activity. This study aimed to develop and validate a method for enalapril and enalaprilat analysis and to determine the bioequivalence of two tablet formulae of enalapril. LC-MS/MS bioanalytical method was developed and validated and then applied to evaluate the bioavailability of two enalapril formulae. Antihyperglycemic sitagliptin was used as internal standard (IS). The method was accurate for the within- and between-days analysis, and precise CV% was <5%, being linear over the calibration range 1.0–200.0 ng/ml. Stability was >85% and the LOD was 0.907 and 0.910 ng/ml for enalapril and enalaprilat, respectively, and LLOQ was 1 ng/ml. The pharmacokinetic parameters Cmax, tmax, AUC0–72, and AUC0–∞ values of enalapril and enalaprilat of the two formulae were calculated and nonsignificant differences were found. A linearity, specific, accurate, and precise method was developed and applied for the analysis of enalapril and enalaprilat in human plasma after oral administration of two formulae of enalapril 20 mg tablets in healthy volunteers. Depending on the statistical analysis it was concluded that the two enalapril formulae were bioequivalent.

scholarly journals The pharmacokinetic interaction between nasally administered naloxone and the opioid remifentanil in human volunteers

2021 ◽  
Author(s):  
Ida Tylleskar ◽  
Sissel Skarra ◽  
Arne Kristian Skulberg ◽  
Ola Dale
Keyword(s):  
Maximum Concentration ◽  
Intranasal Administration ◽  
Area Under The Curve ◽  
Pharmacokinetic Interaction ◽  
Intramuscular Administration ◽  
Nasal Administration ◽  
Pharmacokinetic Studies ◽  
Remifentanil Infusion ◽  
Human Volunteers ◽  
Significant Difference

Abstract Purpose Remifentanil has been shown to increase the bioavailability of nasally administered naloxone. The aim of this study was to explore the nature of this observation. Methods We analysed samples from three pharmacokinetic studies to determine the serum concentrations of naloxone-3-glucuronide (N3G), the main metabolite of naloxone, with or without exposure to remifentanil. To enable direct comparison of the three studies, the data are presented as metabolic ratios (ratio of metabolite to mother substance, N3G/naloxone) and dose-corrected values of the area under the curve and maximum concentration (Cmax). Results Under remifentanil exposure, the time to maximum concentration (Tmax) for N3G was significantly higher for intranasal administration of 71 min compared to intramuscular administration of 40 min. The dose-corrected Cmax of N3G after intranasal administration of naloxone under remifentanil exposure was significantly lower (4.5 ng/mL) than in subjects not exposed to remifentanil (7.8–8.4 ng/mL). The metabolic ratios after intranasal administration rose quickly after 30–90 min and were 2–3 times higher at 360 min compared to intravenous and intramuscular administration. Remifentanil exposure resulted in a much slower increase of the N3G/naloxone ratio after intranasal administration compared to intranasal administration with the absence of remifentanil. After remifentanil infusion was discontinued, this effect gradually diminished. From 240 min there was no significant difference between the ratios observed after intranasal naloxone administration. Conclusion Remifentanil increases the bioavailability of naloxone after nasal administration by reducing the pre-systemic metabolism of the swallowed part of the nasal dose.

Effects of the malononitrilamide FK778 on immune functions in vitro in whole blood from non-human primates and healthy human volunteers

2003 ◽  
Vol 11 (2) ◽  
pp. 163-167 ◽  
Author(s):  
Tudor Bı̂rsan ◽  
Camille Dambrin ◽  
Jochen Klupp ◽  
Mario Stalder ◽  
William E. Fitzsimmons ◽  
...  
Keyword(s):  
Whole Blood ◽  
Immune Functions ◽  
Healthy Human ◽  
Human Volunteers

scholarly journals Excretion of mephedrone and its phase I metabolites in urine after a controlled intranasal administration to healthy human volunteers

2022 ◽  
Author(s):  
Joanna Czerwinska ◽  
Mark C. Parkin ◽  
Claire George ◽  
Andrew T. Kicman ◽  
Paul I. Dargan ◽  
...  
Keyword(s):  
Phase I ◽  
Intranasal Administration ◽  
Healthy Human ◽  
Human Volunteers

Enantioselective Pharmacokinetics of Primaquine in Healthy Human Volunteers

2015 ◽  
Vol 43 (4) ◽  
pp. 571-577 ◽  
Author(s):  
Babu L. Tekwani ◽  
Bharathi Avula ◽  
Rajnish Sahu ◽  
Narayan D. Chaurasiya ◽  
Shabana I. Khan ◽  
...  
Keyword(s):  
Healthy Human ◽  
Human Volunteers ◽  
Enantioselective Pharmacokinetics
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