In vitro and in vivo neuromuscular effects of atracurium and rocuronium in rats treated with carbamazepine for seven days.
OBJECTIVE
This experimental study investigated the in vitro and in vivo neuromuscular blockade of rocuronium and atracurium in rats treated with carbamazepine and determined the concentration of cytochrome P450 and b5 reductase in hepatic microsomes.


METHODS
Rats were treated with carbamazepine (CBZ)--40 mg x kg(-1) by gavage and sacrificed on the eighth day under anesthesia with urethane. In vitro and in vivo preparations followed the techniques of Bulbring and Leeuwin and Wolters, respectively. Concentrations and doses of the neuromuscular blockers used in in vitro and in vivo preparations were, respectively, 20 microg x mL(-1) and 0.5 mg x kg(-1) for atracurium (ATC); and 4 microg x kg(-1) and 0.6 mg x kg(-1) for rocuronium (ROC). Each protocol had an n = 5 and the response was observed for 60 minutes. The effects of ATC and ROC were evaluated in the preparations of rats treated with carbamazepine (CBZ(t)) and compared to those of non-treated rats (CBZ(st)). The concentration of cytochrome P450 and b5 reductase were determined in hepatic chromosomes of rats treated with carbamazepine (CBZ(t)) and non-treated rats (CBZ(st)).


RESULTS
Carbamazepine did not change the amplitude of neuromuscular response; differences in the neuromuscular blockade produced by atracurium in CBZ1 preparations were not observed, in vitro or in vivo, when compared with CBZ(st); the neuromuscular blockade produced by rocuronium in CBZ(t) preparations was potentiated in vitro. Carbamazepine did not change the concentrations of cytochrome P450 and b5.


CONCLUSIONS
Seven-day treatment with carbamazepine did not change the neuromuscular blockade produce by atracurium, but altered the in vitro effects of rocuronium. The duration of the treatment was not enough to cause enzymatic induction and decrease the sensitivity to rocuronium.
de Barcelos
Caroline Coutinho
CC
Departamento de Farmacologia da Faculdade de Ciências Médicas da Unicamp (FCM-UNICAMP), Campinas, SP.
Braga
Angélica de Fátima Assunção
Ade F
Braga
Franklin Sarmento da Silva
FS
Potério
Gloria Braga
GB
Fernandes
Samanta Cristina Antoniassi
SC
Franco
Yoko Oshima
YO
Simioni
Léa Rodrigues
LR
D000732:Androstanols / Q000494:pharmacology*; D000818:Animals; D001279:Atracurium / Q000494:pharmacology*; D002220:Carbamazepine / Q000008:administration & dosage*; D066298:In Vitro Techniques; D009407:Nerve Block; D009469:Neuromuscular Junction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D051381:Rats; D000077123:Rocuronium; D013997:Time Factors
D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D001279:Atracurium; D002220:Carbamazepine; D000077123:Rocuronium