Pharmacokinetics, pharmacodynamics and safety profile of tapentadol hydrochloride injection: a phase 1 dose-escalation study in patients with moderate to severe pain

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Abstract An injectable formulation of tapentadol hydrochloride offers a promising alternative for clinical settings requiring rapid analgesia. However, comprehensive clinical data on the pharmacokinetics (PK), pharmacodynamics (PD), and safety of intravenous tapentadol hydrochloride in patients with pain are currently lacking. Thirty patients with moderate to severe non-cancer pain were enrolled and received single intravenous doses of tapentadol (0.05, 0.15, 0.3, 0.5, or 0.6 mg/kg). PK parameters were derived from plasma concentrations measured via LC-MS/MS. PD effects were assessed using the Numeric Rating Scale (NRS) for pain intensity. Safety was monitored through adverse events (AEs), laboratory tests, and vital signs. Tapentadol exhibited linear pharmacokinetics over the dose range. Mean C max increased from 43.85 ng/mL (0.05 mg/kg) to 402.50 ng/mL (0.6 mg/kg), and mean AUC 0−∞ ranged from 74.20 to 838.27 h·ng/mL. The terminal half-life (t 1/2 ) was consistent (4.09–4.75 h). Pain relief occurred within 15 min and was sustained for up to 24 h across the studied dose range (0.05–0.6 mg/kg). Overall, 83.3% of subjects reported treatment-emergent AEs, most commonly dizziness (40.0%), vertigo (20.0%), and nausea (16.7%). All AEs were mild to moderate except one case of grade III hypertension (0.5 mg/kg), which resolved without intervention. No serious AEs or discontinuations occurred. Tapentadol hydrochloride injection demonstrated dose-proportional pharmacokinetics, rapid analgesic onset, and a tolerable safety profile in patients with moderate to severe pain, supporting its potential as a therapeutic option in acute pain management.

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