Clinical pharmacokinetics after repeated intrapleural bupivacaine administration

Patients (n = 14) who underwent thoracotomy during surgery of the oesophagus for cancer received an initial intrapleural dose of 10 ml bupivacaine hydrochloride 2.5 mg/ml followed by repeated administration every 8 hours from the first to the fourth postoperative day. The mean (+/- SD) peak plasma drug concentration (Cmax) [352 +/- 120 micrograms/L], time to peak (tmax) [0.83 +/- 0.51 h], and first-order absorption rate constant (ka) [5.46 +/- 4.95 h-1] after the twelfth dose were significantly different from the Cmax (206 +/- 81 micrograms/L), tmax (1.8 +/- 1.2h), and ka (1.8 +/- 1.47 h-1) determined after the first dose. Half-life (3.5 +/- 2.2h) and mean concentration (204 +/- 105 micrograms/L) were not significantly different on the fourth day from those on the first (4.1 +/- 2.6h and 142 +/- 71 micrograms/L, respectively). No sharp peak corresponding to systemic toxicity and no accumulation could be expected with these low doses, administered at short intervals and providing good pain relief in this surgical series.