Absorption and pharmacokinetics of bupivacaine after bilateral topical administration in tonsillar fossae for posttonsillectomy pain relief

Pharmacol Res Perspect. 2024 Apr;12(2):e1196. doi: 10.1002/prp2.1196.


No previous studies have investigated the systemic absorption of bupivacaine when used topically for posttonsillectomy pain. The present study was undertaken to investigate the pharmacokinetics of bupivacaine after administration by a swab in the tonsillar fossae over 4 min after tonsillectomy. Eleven adult patients undergoing elective tonsillectomy were recruited. After removal of both tonsils, each of the two tonsillar fossae was covered with a swab moistened with 2 mL of bupivacaine 5 mg/mL, that is, a total of 20 mg bupivacaine. Blood samples were drawn after 0, 5, 10, 20, 30, 45, and 60 min. Bupivacaine was analyzed with an ultra-high-performance liquid chromatography-tandem mass spectrometry method. The highest single measured bupivacaine serum concentration was 23.2 ng/mL and took place 10 min after drug administration. Mean (±SD) Cmax was 11.4 ± 6.0 ng/mL and mean tmax was 11.3 ± 4.7 min. Mean t1/2 was 31.6 ± 9.3 min. As the toxic concentration threshold has been reported to be in the interval 1500-4500 ng/mL, the concentrations measured were well below 2% of the lowest cited toxic threshold. In conclusion, this study shows that applying 4 mL of bupivacaine 5 mg/mL by a swab in the tonsillar fossae posttonsillectomy yields very low plasma concentrations, suggesting its safe application without any risk of systemic toxic effects.

Keywords: bupivacaine; high‐performance liquid chromatography‐tandem mass spectrometry; local anesthesia; systemic absorption; tonsillectomy pain.

MeSH terms

  • Adult
  • Anesthetics, Local / pharmacokinetics
  • Bupivacaine* / pharmacokinetics
  • Humans
  • Pain Measurement
  • Pain, Postoperative / drug therapy
  • Pain, Postoperative / etiology
  • Tonsillectomy* / adverse effects
  • Tonsillectomy* / methods


  • Bupivacaine
  • Anesthetics, Local