Tapentadol Versus Tramadol: A Narrative and Comparative Review of Their Pharmacological, Efficacy and Safety Profiles in Adult Patients.

We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical interest of tapentadol in adult patients. Tapentadol and tramadol share a mixed mechanism of action, including both mu-agonist and monoaminergic properties. Tapentadol is approximately two to three times more potent than tramadol and two to three times less potent than morphine. It has no identified analgesically active metabolite and is not significantly metabolised by cytochrome P450 enzymes, thus overcoming some limitations of tramadol, including the potential for pharmacokinetic drug-drug interactions and interindividual variability due to genetic polymorphisms of cytochrome P450 enzymes. The toxicity profiles of tramadol and tapentadol are similar; however tapentadol is likely to result in less exposure to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) but cause more opioid adverse effects (constipation, respiratory depression, abuse) than tramadol. The safety of tapentadol in real-world conditions remains poorly documented, particularly in at-risk patient subgroups and also in the ability to assess the risk associated with its residual serotonergic activity (serotonin syndrome, seizures). Because of an earlier market introduction, more real-world safety data are available for tramadol, including data from at-risk patient subgroups. The level of evidence on the efficacy of both tramadol and tapentadol for the treatment of chronic pain is globally low. The trials published to date show overall that tapentadol does not provide a clinically significant analgesic improvement compared to existing treatments, for which the safety profile is much better known. In conclusion, tapentadol is not a first-line opioid but represents an additional analgesic in the therapeutic choices, which some patients may benefit from after careful examination of their clinical situation, co-morbidities and co-medications.

Pharmacokinetic Analysis, Analgesic Effects, and Adverse Effects of Tapentadol in Cancer Patients with Pain.

In this study, we conducted a pharmacokinetic analysis of tapentadol (TP) in Japanese patients with cancer pain and identified covariates influencing pharmacokinetic parameters. In addition, the analgesic effects and adverse effects of TP were investigated. Data were collected from in-patients with cancer pain who had been administered TP as an extended-release formula. The median (range) estimated clearance (CL/F) and distribution volume (Vd/F) of TP were 86.7 (31.3-213.7) L/h and 1288 (189-6736) L, respectively. There was a strong negative correlation between CL/F and age, Child-Pugh score, and albumin-bilirubin (ALBI) score. The subjects were further divided into two groups according to the factors highly correlated with CL/F. The CL/F of patients in the Child-Pugh B group was 0.46-times that of patients in the Child-Pugh A group. In addition, the CL/F of patients with an ALBI score > -2.40 was 0.56-times that of patients with ALBI scores ≤-2.40, and both differences were statistically significant (p < 0.05). The mean intensity of pain over 24 h was investigated daily from before starting TP for the first 7 d of the treatment. TP reduced pain in six of nine patients; the mean pain visual analogue scale score decreased significantly from 59.2 mm before administration to 42.5 mm at days 5-7. Overall, the Child-Pugh and ALBI scores significantly affected the clearance of TP, which was reduced in patients with impaired liver function. These results suggest that TP is an opioid with a sufficient analgesic effect for cancer patients.

Quantitation of Tapentadol by Liquid Chromatography: Tandem Mass Spectrometry.

Tapentadol is an orally active analgesic with a similar structure to tramadol. Its primary mechanism of action is agonist action on the mu-opioid receptor. The method described here quantitates tapentadol in the whole blood using a matching deuterated internal standard, extraction via a protein "crash" with acetonitrile, followed by analysis using liquid chromatography-tandem mass spectrometry.

Improved therapeutic potential of tapentadol employing cationic exchange resins as carriers in neuropathic pain: evidence from pharmacokinetic and pharmacodynamics study.

Current investigation was endeavoured to overcome problem of poor palatability and bioavailability of centrally acting analgesic, tapentadol (TAP) by formulating controlled release drug-resin complexes (DRCs). The technology encompassed in preparation of DRCs involved chemisorption of TAP to weak cationic resins (KyronT-134 and Tulsion335) by batch method. Various formulation variables like drug-resin ratio, pH, resin activation and swelling time were optimized to achieve maximum drug loading in DRCs. FT-IR, DSC, pXRD, in vitro release study under bio-relevant condition of mouth and in vivo sensory taste evaluation established formation of taste masked DRC whereas dissolution study assured prolonged drug release behaviour of optimized DRC. Among DRCs, TAP-KyronT-134 complex exhibited higher drug loading (80.89 ± 4.56%), stability and prolonged release profile (10 h) without any detectable amount of drug release under salivary conditions. Pharmacokinetic studies in wistar rats revealed increased Tmax (2.67-fold), MRT (1.94-fold), elimination half-life (2.79-fold) and relative oral bioavailability (2.62-fold) of TAP on oral administration of optimized formulation compared to TAP solution. Furthermore, pharmacodynamics study confessed higher potential of DRC in attenuating chronic injury induced tactile allodynia for prolonged duration. In conclusion, the method developed is easily scalable and holds potential for commercialization with an evidence of obtaining more efficacious neuropathic pain management therapy.

Pharmacokinetics of tapentadol in laying hens and its residues in eggs after multiple oral dose administration.

1. The aim of the study was to evaluate the pharmacokinetics (PKs) of tapentadol (TAP), a novel opioid analgesic, in laying hens after intravenous (IV) and oral (PO) administration and to quantify the concentrations of TAP residues in eggs. 2. Twenty healthy laying hens were divided into three groups: A (n = 6), B (n = 6) and C (n = 8). The study was conducted in two phases. Groups A and B received TAP by IV and PO routes at the dose of 1 and 5 mg/kg, respectively. 3. No visible adverse effects were observed after administration of the drug. TAP plasma concentrations were detectable up to 4 h following administration. Following IV administration, TAP plasma concentrations were only higher than the minimal effective concentration (148 ng/ml) reported for humans for 1 h. After single PO administration, plasma concentrations of TAP would not conform to software algorithms and the PK parameters were not calculated. TAP concentration following multiple PO doses at 5 mg/kg for 5 d was found to be higher and more persistent (12 h vs. 7 h) in yolk compared with albumen. 4. This is the first PK study on the novel atypical opioid TAP in laying hens. Further studies are required to investigate the analgesic efficacy and actual effective plasma concentration of TAP in this species.