title: Clinical pharmacokinetics after repeated intrapleural bupivacaine administration.
abstract: 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.
authors.affiliation: Laboratory of Pharmacology, University Hospital Centre, Caen, France.
authors.forename: D
authors.initials: D
authors.lastname: Debruyne
authors.forename: M A
authors.initials: MA
authors.lastname: Moulin
authors.forename: J
authors.initials: J
authors.lastname: Tartiere
authors.forename: M C
authors.initials: MC
authors.lastname: Bigot
authors.forename: J L
authors.initials: JL
authors.lastname: Gerard
authors.forename: H
authors.initials: H
authors.lastname: Bricard
mesh_terms: D000328:Adult; D000368:Aged; D002045:Bupivacaine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy*; D010994:Pleura; D013908:Thoracotomy
chemical_list: D002045:Bupivacaine