Clinical Pharmacokinetics After Repeated Intrapleural Bupivacaine Administration

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Abstract
Patients (n = 14) who underwent thoracotomy during surgery of the oesophagus for cancer received an initial intrapleural dose of 10ml 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 μg/L], time to peak (tmax) [0.83 ± 0.51h], 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 μg/L). tmax (1.8 ± 1.2h), and ka (1.8 ± 1.47 h−1) determined after the first dose. Halflife (3.5 ± 2.2h) and mean concentration (204 ± 105 μg/L) were not significantly different on the fourth day from those on the first (4.1 ± 2.6h and 142 ± 71 μg/L, respectively). No sharp peak corresponding to sytemic toxicity and no accumulation could be expected with these low doses, administered at short intervals and providing good pain relief in this surgical series.