Postmortem Distribution of Tapentadol and N-Desmethyltapentadol

Abstract

Postmortem distribution concentrations of the pain medication tapentadol and its metabolite N-desmethyltapentadol are reported. Tapentadol (Nucynta®) is a synthetic mu-opioid receptor agonist that also has norepinephrine reuptake inhibitor action. The laboratory received two cases. Case 1: a 19-year-old, morbidly obese male with sudden unexpected death. Toxicology results revealed tapentadol (femoral blood: 0.77 mg/L, liver: 1.65 mg/kg), N-desmethyltapentadol (femoral blood: 0.07 mg/L, liver: 0.19 mg/kg), diazepam (femoral blood: 0.04 mg/L), nordiazepam (femoral blood: 0.06 mg/L) and amiodarone (femoral blood: 5.30 mg/L). Case 2: a 60-year-old female who died from complications following hip replacement. Only tapentadol (femoral blood: 0.26 mg/L, liver: 0.52 mg/kg) was found in the toxicology results. Quantitative results of tapentadol/N-desmethyltapentadol were achieved using liquid chromatography-tandem mass spectrometry in multiple reactions monitoring mode. This is the first known distribution study of tapentadol and N-desmethyltapentadol values in postmortem cases.

Comparative study of the neurotoxicological effects of tramadol and tapentadol in SH-SY5Y cells

“…In the same way, fatal intoxications by tramadol (Clarkson et al 2004;Costa et al 2013;Shadnia et al 2008) and tapentadol (Kemp et al 2013;Larson et al 2012) have been described, for which it is important to evaluate their toxicity, and its corresponding mechanisms.…”

“…In order to understand what happens in extreme situations, such as intoxication and fatal cases, high concentrations of both opioids were used Kemp et al 2013;Larson et al 2012;Shadnia et al 2008). Indeed, in therapeutic doses (single oral dose of 100mg) maximum serum concentrations (Cmax) were approximately 1M for tramadol (Grond and Sablotzki 2004;Raffa et al 2012) and 0.5M for tapentadol (Raffa et al 2012 …”

“…Their clinical interest is mostly due to their low incidence of side effects, when compared with classical opioids such as heroin and morphine (Hartrick and Rozek 2011). Nevertheless, respiratory depression and fatal intoxications have been reported for these compounds Dinis-Oliveira et al 2012a;Dinis-Oliveira et al 2012b;Larson et al 2012;Pinho et al 2013;Ryan and Isbister 2015), and brain lesions were found in one subject with a history of tramadol abuse in a study that analysed 28 subjects (Boostani and Derakhshan 2012). Although serotonin syndrome is often associated with the consumption of tramadol, a recent study by Ryan and Isbister did not detect serotonin toxicity in overdose cases with tramadol (Ryan and Isbister 2015;Sansone and Sansone 2009).…”

“…Regarding postmortem, tramadol and tapentadol concentrations are highly variable. Indeed, tramadol concentrations of 7.7 mg/L and 48.34 mg/L were reported, while 3.2 mg/L and 0.77 mg/L were found for tapentadol in postmortem blood samples De Backer et al 2010;Kemp et al 2013;Larson et al 2012). Thus, given the variability in maximum postmortem blood concentrations, our aim was to ascertain the damage extent in a broader concentration range.…”

Review of Post-Marketing Safety Data on Tapentadol, a Centrally Acting Analgesic

“…Three fatal cases were reported; all patients had concomitantly taken opioid analgesics or benzodiazepines. One of the patients had the additional risk factors obesity, sleep apnea, asthma, and COPD [41]; another was a cancer patient. The third patient had pulmonary edema and a peritonsillar abscess; infectious mononucleosis was stated as cause of death.…”