Recirculatory pharmacokinetics and pharmacodynamics of rocuronium in patients - The influence of cardiac output

Background: Recirculatory models are capable of accurately describing first -pass pharmacokinetics and the influence of cardiac output (CO), which is i mportant for drugs with a fast onset of effect. The influence of CO on phar macokinetic and pharmacodynamic parameters of rocuronium in patients was ev aluated using a recirculatory pharmacokinetic model. Methods: Fifteen patients were included to study rocuronium pharmacokinetic s and pharmacodynamics. Bolus doses of rocuronium (0.35 mg/kg) and indocyan ine green (25 mg) were injected simultaneously via a peripheral intravenous catheter. Blood samples were taken for 240 min from the radial artery. The force of contraction of the adductor pollicis after a train-of-four at 2 H z every 12 s was measured. Arterial concentration-time curves of rocuronium and indocyanine green were analyzed using a recirculatory model. Pharmacod ynamics were described using a sigmoid maximum effect (E-max) model. Results: The CO of the patients varied from 2.43 to 5.59 1/min. Total distr ibution volume of rocuronium was 17.3 +/- 4.8 1 (mean +/- SD). The CO showe d a correlation with the fast tissue clearance (ClT-f; r(2) = 0.51), with t he slow tissue clearance (ClT-s; r(2) = 0.31) and with the mean transit tim es of rocuronium except for the mean transit time of the slow tissue compar tment. The blood-effect site equilibration constant (k(e0)) was strongly co rrelated with CO (r(2) = 0.70). Conclusions: Cardiac output influences the pharmacokinetics, including k(e0 ), for rocuronium in patients. For drugs with a fast onset of effect, a rec irculatory model, which includes CO, can give a good description of the rel ation between concentration and effect, in contrast to a conventional compa rtmental pharmacokinetic model.