Pharmacokinetics and pharmacodynamics of vecuronium in children receiving phenytoin or carbamazepine for chronic anticonvulsant therapy

The pharmacokinetics and time course of action of vecuronium in normal chil dren and children receiving anticonvulsant drugs for prolonged periods were characterized. A bolus dose of vecuronium 0.15 mg kg(-1) was administered i.v. to 10 non-epileptic children and to 10 children on phenytoin and 10 ch ildren on carbamazepine, who were matched for age and weight. Plasma concen trations of vecuronium, 3-OH desacetylvecuronium (the primary metabolite of vecuronium) and at-acid glycoprotein (AAG) were determined. Pharmacokineti c variables were derived from plasma samples collected before and after adm inistration of vecuronium. Neuromuscular transmission was monitored by evok ed compound electromyography. Recovery of the first twitch of the train-of- four (T-1/T-0) and the recovery index (RI), the time for 25-75% recovery of T-1/T-0, were determined. The elimination half-life of vecuronium was sign ificantly reduced in both anticonvulsant groups compared with control [cont rol 48.2 (SD 40.3), phenytoin 23.5 (13.1), carbamazepine 18.4 (16.6) min, P <0.05]. Vecuronium clearance was increased in both anticonvulsant groups [c ontrol 9.0 (3.6), phenytoin 15.1 (8.9), carbamazepine 18.8 (13.1) ml kg(-1) min(-1), 0.05<P<0.1]. Children on chronic anticonvulsant therapy had a sig nificantly shorter RI than control [control 21.8 (11), phenytoin 12.5 (8.3) , carbamazepine 10.6 (5.9) min, P<0.05]. Concentrations of vecuronium at di fferent degrees of recovery of TI, volumes of distribution and AAG concentr ations were not different between groups. Our data confirm anticonvulsant-i nduced resistance to vecuronium in children and support a pharmacokinetic c omponent contributing to the resistance.