Pharmacodynamic modelling of rocuronium in adolescents with Duchenne muscular dystrophy

Background and objective Studies with rocuronium showed a delayed onset and prolonged recovery in patients with Duchenne muscular dystrophy (DMD). The objective of this study was to identify the pharmacokinetic and/or pharmacodynamic origin of these alterations. Methods Twenty-five male patients (15 with DMD, 10 controls, aged 10–18 years) were studied. Patients were anaesthetized with propofol and sufentanil. Neuromuscular transmission was monitored by acceleromyography. Patients received a single intravenous dose of 0.3 mg kg−1 rocuronium. In five patients of the DMD group, pharmacokinetic modelling was performed from arterial rocuronium concentrations. The time course of neuromuscular block was analysed with a sigmoid Emax model including an effect compartment. Results The pharmacokinetics of rocuronium in DMD patients were Vc 63 ± 14 ml kg−1, Cl 3.0 ± 1.0 ml min−1 kg−1, half-lives 2.0 ± 0.6, 20 ± 10 and 129 ± 98 min, SE. For both the DMD and the control group, the time course of neuromuscular block could be described by a sigmoid Emax model using the estimated pharmacokinetic parameters of the DMD group. In patients with DMD, the equilibration between the central and effect compartment was significantly slower (T1/2ke0: 9.7 ± 0.3 vs. 1.3 ± 0.1 min) and the EC50 was significantly smaller (512 ± 20 vs. 1170 ± 64 ng ml−1), whereas the ED50 was 0.16 ± 0.02 mg kg−1 in both groups. Conclusion The pharmacodynamics of rocuronium were significantly altered in patients with DMD, whereas the pharmacokinetics seemed to be similar to those in healthy adults. Patients with DMD were more sensitive with respect to effect site concentration but not with respect to dose.