Pharmacokinetics and Pharmacodynamics of 3 Doses of Oral-Mucosal Dexmedetomidine Gel for Sedative Premedication in Women Undergoing Modified Radical Mastectomy for Breast Cancer

BACKGROUND: Buccal dexmedetomidine (DEX) produces adequate preoperative sedation and anxiolysis when used as a premedication. Formulating the drug as a gel decreases oral losses and improves the absorption of buccal DEX. We compared pharmacokinetic and pharmacodynamic properties of 3 doses of buccal DEX gel formulated in our pharmaceutical laboratory for sedative premedication in women undergoing modified radical mastectomy for breast cancer. METHODS: Thirty-six patients enrolled in 3 groups (n = 12) to receive buccal DEX gel 30 minutes before surgery at 0.5 mu g/kg (DEX 0.5 group), 0.75 mu g/kg (DEX 0.75 group), or 1 mu g/kg (DEX 1 group). Assessments included plasma concentrations of DEX, and pharmacokinetic variables calculated with noncompartmental methods, sedative, hemodynamic and analgesic effects, and adverse effects. RESULTS: The median time to reach peak serum concentration of DEX (T-max) was significantly shorter in patients who received 1 mu g/kg (60 minutes) compared with those who received 0.5 mu g/kg (120 minutes; P = .003) and 0.75 mu g/kg (120 minutes; P = .004). The median (first quartile-third quartile) peak concentration of DEX (maximum plasma concentration [C-max]) in plasma was 0.35 ng/mL (0.31-0.49), 0.37 ng/mL (0.34-0.40), and 0.54 ng/mL (0.45-0.61) in DEX 0.5, DEX 0.75, and DEX 1 groups (P = .082). The 3 doses did not produce preoperative sedation. The 1 mu g/kg buccal DEX gel produced early postoperative sedation and lower intraoperative and postoperative heart rate values. Postoperative analgesia was evident in the 3 doses in a dose-dependent manner with no adverse effects. CONCLUSIONS: Provided that it is administered 60-120 minutes before surgery, sublingual administration of DEX formulated as an oral-mucosal gel may provide a safe and practical means of sedative premedication in adults.

Automated summary

This study compared the pharmacokinetic and pharmacodynamic properties of different doses of buccal DEX gel in female patients undergoing modified radical mastectomy for breast cancer. The results showed that the 1 µg/kg dose of buccal DEX gel produced early postoperative sedation, lower heart rate values, and dose-dependent postoperative analgesia. Administering DEX formulated as an oral-mucosal gel sublingually 60-120 minutes before surgery may provide a safe and practical means of sedative premedication in adults.