Recirculatory pharmacokinetics and pharmacodynamics of rocuronium in patients: the influence of cardiac output

Anesthesiology. 2001 Jan;94(1):47-55. doi: 10.1097/00000542-200101000-00012.

Abstract

Background: Recirculatory models are capable of accurately describing first-pass pharmacokinetics and the influence of cardiac output (CO), which is important for drugs with a fast onset of effect. The influence of CO on pharmacokinetic and pharmacodynamic parameters of rocuronium in patients was evaluated using a recirculatory pharmacokinetic model.

Methods: Fifteen patients were included to study rocuronium pharmacokinetics and pharmacodynamics. Bolus doses of rocuronium (0.35 mg/kg) and indocyanine 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 Hz every 12 s was measured. Arterial concentration-time curves of rocuronium and indocyanine green were analyzed using a recirculatory model. Pharmacodynamics were described using a sigmoid maximum effect (Emax) model.

Results: The CO of the patients varied from 2.43 to 5.59 l/min. Total distribution volume of rocuronium was 17.3 +/- 4.8 l (mean +/- SD). The CO showed a correlation with the fast tissue clearance (Cl(T_f); r2 = 0.51), with the slow tissue clearance (Cl(T_s); r2 = 0.31) and with the mean transit times of rocuronium except for the mean transit time of the slow tissue compartment. The blood-effect site equilibration constant (k(e0)) was strongly correlated with CO (r2 = 0.70).

Conclusions: Cardiac output influences the pharmacokinetics, including k(e0), for rocuronium in patients. For drugs with a fast onset of effect, a recirculatory model, which includes CO, can give a good description of the relation between concentration and effect, in contrast to a conventional compartmental pharmacokinetic model.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Androstanols / pharmacokinetics*
  • Androstanols / pharmacology
  • Anesthesia, General*
  • Anesthetics, Intravenous*
  • Cardiac Output*
  • Coloring Agents / pharmacokinetics
  • Female
  • Humans
  • Indocyanine Green / pharmacokinetics
  • Injections, Intravenous
  • Metabolic Clearance Rate
  • Middle Aged
  • Models, Biological*
  • Neuromuscular Depolarizing Agents / pharmacokinetics*
  • Neuromuscular Depolarizing Agents / pharmacology
  • Piperidines*
  • Remifentanil
  • Rocuronium

Substances

  • Androstanols
  • Anesthetics, Intravenous
  • Coloring Agents
  • Neuromuscular Depolarizing Agents
  • Piperidines
  • Indocyanine Green
  • Remifentanil
  • Rocuronium