scholarly journals Methadone, Buprenorphine, Oxycodone, Fentanyl, and Tramadol in Multiple Postmortem Matrices

2021 ◽  
Author(s):  
Stine Marie Havig ◽  
Vigdis Vindenes ◽  
Åse Marit Leere Øiestad ◽  
Sidsel Rogde ◽  
Cecilie Hasselø Thaulow
Keyword(s):  
Peripheral Blood ◽  
Vitreous Humor ◽  
Pericardial Fluid ◽  
Limited Information ◽  
Blood Concentrations ◽  
Bodily Fluids ◽  
Drug Concentrations ◽  
Quantitative Analyses ◽  
Alternative Matrices ◽  
Almost All

Abstract Peripheral blood concentrations are generally preferred for postmortem toxicological interpretation, but some autopsy cases may lack blood for sampling due to decomposition or large traumas etc. In such cases, other tissues or bodily fluids must be sampled; however, limited information exists on postmortem concentrations in matrices other than blood. Pericardial fluid, muscle, and vitreous humor have been suggested as alternatives to blood, but only a few studies have investigated the detection of opioids in these matrices. In this study, we aimed to investigate the detection of methadone, buprenorphine, oxycodone, fentanyl, and tramadol in postmortem samples of pericardial fluid, skeletal muscle, and vitreous humor, in addition to peripheral and cardiac blood; and if drug concentrations in these alternative matrices were comparable to those in peripheral blood, and thereby useful for interpretation. In most of the 54 included cases, only one opioid was detected. Methadone, oxycodone, fentanyl, and tramadol were detected in all of the alternative matrices in almost all cases, while buprenorphine was detected less often. For methadone, the concentrations in the alternative matrices, except for in vitreous humor, were relatively similar to those in peripheral blood. Larger variations in concentrations were found for buprenorphine, oxycodone, and tramadol. Quantitative analyses appeared useful for fentanyl, in all of the alternative matrices, but only four cases were included. Toxicological analyses of opioids in these alternative postmortem matrices can be useful for detection, but interpretation of quantitative results must be performed with caution.

scholarly journals Acidic Drug Concentrations in Postmortem Vitreous Humor and Peripheral Blood

2019 ◽  
Author(s):  
Jacqueline A Hubbard ◽  
Aylmer L Navarrete ◽  
Robert L Fitzgerald ◽  
Iain M McIntyre
Keyword(s):  
Peripheral Blood ◽  
High Performance ◽  
Vitreous Humor ◽  
Vitreous Fluid ◽  
Over The Counter ◽  
Acidic Drugs ◽  
Drug Concentrations ◽  
Postmortem Toxicology ◽  
Potential Alternative ◽  
Array Detection

Abstract Vitreous humor is a potential alternative matrix for postmortem toxicology drug screens when peripheral blood is unavailable. It is easily and reliably collected and may not suffer from the same postmortem redistribution as seen in blood. Here, we compared the concentrations of 7 acidic drugs (acetaminophen, ibuprofen, naproxen, salicylic acid, carbamazepine, phenobarbital and phenytoin) in peripheral blood and vitreous fluid collected in 89 autopsy cases. Analysis was done by high-performance liquid chromatography with diode-array detection. Overall, we found that vitreous drug concentrations were significantly lower than peripheral blood with median vitreous to peripheral blood (V/PB) ratios ranging from 0.0 to 0.6 (mean, 0.1–0.6). The correlations between the concentrations of over-the-counter analgesics in peripheral blood versus vitreous fluid were poor, with acetaminophen exhibiting the best linearity (R2 = 0.72). The antiepileptic drugs (carbamazepine, phenytoin and phenobarbital) exhibited good correlations between peripheral blood and vitreous humor, with all exhibiting an R2 ≥ 0.95. Overall, we have demonstrated the potential of vitreous fluid as an alternative matrix for the detection of select acidic drugs.

scholarly journals Post mortem changes: challenges in drug analysis in the diagnosis of deaths from intoxication

2021 ◽  
Vol 5 (1) ◽  
pp. 14-18
Author(s):  
Marina Camargo Galera ◽  
Luciana Grazziotin Rossato-Grando
Keyword(s):  
Forensic Toxicology ◽  
Vitreous Humor ◽  
Forensic Analysis ◽  
Drug Analysis ◽  
Biochemical Changes ◽  
Post Mortem ◽  
Postmortem Redistribution ◽  
Pubmed Database ◽  
Quantitative Analyses ◽  
Alternative Matrices

In forensic toxicology, alternative matrices and sampling sites are required for a correlation of antemortem and postmortem concentrations with the least possible error. Postmortem redistribution phenomena and biochemical changes inherent to these processes are possible, and represent interferences in these analyses. This study aimed to perform a bibliographic review through Pubmed database within a 10-year period of time, using the keywords: forensic analysis AND redistribution. We observed that for quantitative analyses the preferred matrix is blood from peripheral vessels, and when it is not available, vitreous humor is a great specimen for choice. 

scholarly journals Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression

2021 ◽  
Vol 22 (3) ◽  
pp. 1022
Author(s):  
Tatyana P. Makalish ◽  
Ilya O. Golovkin ◽  
Volodymyr V. Oberemok ◽  
Kateryna V. Laikova ◽  
Zenure Z. Temirova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Rat Model ◽  
Peripheral Blood ◽  
Antisense Oligonucleotide ◽  
Joint Inflammation ◽  
Blood Concentrations ◽  
Tnf Α ◽  
Effective Drugs ◽  
First Time

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund’s adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.

Interpretation of drug concentrations in an alternative matrix: the case of meprobamate in vitreous humor

2011 ◽  
Vol 125 (3) ◽  
pp. 463-468 ◽  
Author(s):  
Fabien Bévalot ◽  
Marie-Paule Gustin ◽  
Nathalie Cartiser ◽  
Catherine Le Meur ◽  
Daniel Malicier ◽  
...  
Keyword(s):  
Vitreous Humor ◽  
Drug Concentrations

Buprenorphine blood concentrations: A biomarker for analgesia

2021 ◽  
Vol 17 (7) ◽  
pp. 15-20
Author(s):  
Michael Guarnieri, PhD, MPH
Keyword(s):  
Clinical Evidence ◽  
Acute Postoperative Pain ◽  
Blood Concentrations ◽  
Patient Reports ◽  
Drug Concentrations ◽  
Subjective Pain ◽  
Nonopioid Analgesics ◽  
Pain Reports ◽  
Quantitative Sensory Tests ◽  
Sensory Tests

Opioids, the frontline drugs for postsurgical analgesia, have been linked to diversion and abuse with lethal consequences. The search for safe analgesics with less harm potential has been decades long. However, clinical trials for safe opioid and nonopioid analgesics have relied on subjective pain reports, which are biased by placebo effects that increase the complexity of trials to develop new therapies to manage pain.Research in opioid naïve animals and humans demonstrates that blood concentrations of opioids that effectively saturate the morphine opioid receptor are tightly linked with patient reports and quantitative sensory tests for analgesia. Opioid drug concentrations can predict clinical responses.This report reviews preclinical and clinical evidence correlating buprenorphine pharmacokinetics with analgesia. More than 30 years of data confirm buprenorphine blood concentrations can be an objective biomarker of analgesia for moderate to severe acute postoperative pain.

scholarly journals Drug plasma trough concentrations during treatment with daclatasvir and sofosbuvir are associated respectively with liver impairment and with renal dysfunction in HIV/HCV co-infected patients

2019 ◽  
Author(s):  
Ilaria Mastrorosa ◽  
Massimo Tempestilli ◽  
Stefania Notari ◽  
Patrizia Lorenzini ◽  
Gabriele Fabbri ◽  
...  
Keyword(s):  
Renal Dysfunction ◽  
Virologic Response ◽  
Patient Treatment ◽  
Limited Information ◽  
Plasma Drug ◽  
Related Factors ◽  
Immunological Parameters ◽  
Liver Impairment ◽  
Drug Concentrations ◽  
Plasma Drug Concentrations

Abstract Background Sofosbuvir (SOF) plus daclatasvir (DCV) achieved high rates of sustained virologic response (SVR) with no difference according to HIV serostatus. Only limited information is available on the pharmacokinetics variability of SOF and DCV in HIV/HCV co-infected patients. Aim was to evaluate the association of plasma drug concentrations (Ctrough) of SOF and of DCV with patient-, treatment-, and disease-related factors in the real-world setting of HIV/HCV co-infected persons. Methods HIV/HCV co-infected patients, undergoing SOF plus DCV treatment, were prospectively enrolled. At baseline, week4 (W4), end of treatment (EOT), and after-EOT, biochemical and viro-immunological parameters were assessed. FIB-4 score and CKD-EPI equation were used for estimation of liver disease and glomerular filtration rate (eGFR), respectively. SOF, SOF metabolite (GS-331007), and DCV Ctrough were measured at W4 and week8 (W8), and the mean value (mean-Ctrough) was calculated Results Thirty-five patients were included (SVR 94%). Increasing GS-331007 mean-Ctrough significantly correlated with decreasing eGFR at W4 (rho=-0.36; p=0.037) and EOT (rho=-0.34; p=0.048). Between DCV mean-Ctrough and FIB-4, a significant correlation was observed at all time-points: baseline (rho=-0.35; p=0.037), W4 (rho=-0.44; p=0.008), EOT (rho=-0.40; p=0.023), after-EOT (rho=-0.39; p=0.028). Conclusion In HIV/HCV co-infected patients receiving SOF plus DCV, plasma drug concentrations are associated with renal dysfunction for GS-331007 and with liver impairment for DCV. Though clinical and therapeutically relevance of these findings may apparently be limited, growth of clinicians’ knowledge on DAA exposure in difficult-to-treat patients, as cirrhotic and renal impaired subjects, can be relevant in single cases.

“The Effect of Obstructive Sleep Apnea on Peripheral Blood Amino Acid and Biogenic Amine Metabolome at Multiple Time Points Overnight“

2020 ◽  
Author(s):  
Ott Kiens ◽  
Egon Taalberg ◽  
Viktoria Ivanova ◽  
Ketlin Veeväli ◽  
Triin Laurits ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Amino Acid ◽  
Sleep Apnea ◽  
Biogenic Amines ◽  
Peripheral Blood ◽  
Apnea Hypopnea Index ◽  
Multiple Time ◽  
Blood Concentrations ◽  
Time Points ◽  
Obstructive Sleep

Abstract There are no clinical studies that have investigated the differences in blood serum metabolome between obstructive sleep apnea (OSA) patients and controls. In a single-center prospective observational study, we compared metabolomic profiles in the peripheral blood of OSA patients with apnea-hypopnea index (AHI) > 15/h and control individuals. Blood was obtained at 3 different time points overnight: 21:00 p.m.; 5:00 a.m. and 7:00 a.m. We used a targeted approach for detecting amino acids and biogenic amines and analyzed the data with ranked general linear model for repeated measures. We recruited 31 patients with moderate-to-severe OSA and 32 controls. Significant elevations in median concentrations of alanine, proline and kynurenine in OSA patients compared to controls were detected. Significant changes in the overnight dynamics of peripheral blood concentrations occurred in OSA: glutamine, serine, threonine, tryptophan, kynurenine and glycine levels increased, whereas a fall occurred in the same biomarker levels in controls. Phenylalanine and proline levels decreased slightly, compared to a steeper fall in controls. The study indicates that serum profiles of amino acid and biogenic amines are significantly altered in patients with OSA referring to vast pathophysiologic shifts reflected in the systemic metabolism.

scholarly journals Tolerability, kinetics, and efficacy of subconjunctival pefloxacin in pigmented rabbits.

1995 ◽  
Vol 39 (4) ◽  
pp. 834-838 ◽  
Author(s):  
S Marrakchi-Benjaafar ◽  
I Cochereau ◽  
F D'Hermies ◽  
J J Pocidalo
Keyword(s):  
Half Life ◽  
Maximum Concentration ◽  
High Performance ◽  
Histopathological Examination ◽  
Vitreous Humor ◽  
Subconjunctival Injection ◽  
Corneal Ulcers ◽  
Drug Concentrations ◽  
Pigmented Rabbits ◽  
The Right

Pefloxacin has been shown to have good intraocular penetration when given systemically. In order to extend its clinical use, we have assessed the tolerability, kinetics, and efficacy of subconjunctival pefloxacin in phakic pigmented rabbits. The tolerability of a single subconjunctival injection of pefloxacin (0.8, 1.6, 8, or 16 mg in 0.2 ml) in the right eyes of eight rabbits was evaluated by clinical and histopathological examination. The 0.8-mg dose of pefloxacin was well tolerated. The kinetics was evaluated after a single subconjunctival injection of 0.8 mg in 18 rabbits. Animals were sacrificed at 1, 3, 5, 7, 12, or 18 h postinjection. Drug concentrations were measured by high-performance liquid chromatography. Pefloxacin was found in the cornea (maximum concentration, 18.13 micrograms/ml; half-life, 3.92 h) and in the aqueous humor (maximum concentration, 3.40 micrograms/ml; half-life, 2.14 h). Pefloxacin did not penetrate into the vitreous humor by this route. The efficacy was evaluated in an experimental model of staphylococcal corneal ulcers in eight rabbits which received two subconjunctival injections of 0.8 mg of pefloxacin at 16 and 24 h after intrastromal inoculation. The results (expressed as mean log10 CFU per milliliter +/- standard deviation) showed that pefloxacin significantly (P < 0.001) reduced the bacterial counts (4.39 +/- 0.97) compared with those in control eyes (6.46 +/- 0.69). For phakic eyes, subconjunctival pefloxacin might be of value for the treatment of corneal ulcers. Further studies are required to determine its penetration into the vitreous humor of aphakic eyes.

scholarly journals SMOKING GENOTOXICITY IN PERIPHERAL BLOOD LYMPHOCYTES USING THE COMET ASSAY

2013 ◽  
Vol 03 (03) ◽  
pp. 038-041
Author(s):  
Shobha S. Shetty ◽  
Hrishikesh Nachane
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
The Body ◽  
P Value ◽  
Tail Moment ◽  
Blood Lymphocytes ◽  
Significant Difference ◽  
Almost All

Abstract Background: Smoking has been shown to have a positive effect on DNA damage in almost all the cells of the body. Quantitative analysis of this damage will help in assessing the etiopathogenesis of various nicotine induced damage to the body. Comet assay has been an emerging tool in this regard and hence was applied by us to estimate the severity of DNA damage in smokers. Aims & Objectives: To evaluate the DNA genotoxicity in peripheral blood lymphocytes in smokers and their comparison with non smokers & assess the quantitative damage. Materials and methods: 30 smokers & 20 non smokers were recruited & their peripheral blood was taken for the comet assay to look for Olive moment & Tail moment to quantitatively assess the DNA damage due to cigarette smoking. Results: In our study there was no significant difference in the analysis of DNA damage (with regard to tail moment & olive moment) in smokers versus non smokers (P value: more than 0.05). Conclusions: Though smoking is known to cause DNA damage, we did not find significant differences between the two groups probably due to other multifactorial etiologies for genotoxicity.

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