Pharmacokinetics of Org Nc45 (Norcuron) in Patients With and Without Renal Failure

Abstract

To determine the influence of renal failure on the pharmacokinetics and neuromuscular blockade of Org NC 45 (Norcuron), a new monoquaternary homologue of pancuronium, 13 patients under halothane and nitrous oxide anesthesia were studied. Org NC 45 was administered by 2-min infusion in doses of 0.28 mg kg-1 (normal renal function group, n = 4) and 0.14 mg kg-1 (renal failure group, n = 5). Four additional patients with normal renal function were given Org NC 45 0.14 mg kg-1 to determine the onset, duration and recovery rate of neuromuscular blockade. The serum concentration of Org NC 45 was determined by normal-phase high performance liquid chromatography (sensitivity 50 ng ml-1), and a two-compartment open pharmacokinetic model was fitted to resulting data. Estimates of distribution half-life (T 1/2 alpha), elimination half-life (T 1/2 beta), volume of distribution at steady state (Vss) and clearance of Org NC 45 did not differ significantly between patients with normal renal function and those with renal failure. The onset, duration and recovery rate times of the neuromuscular blockade by Org NC 45 0.14 mg kg-1 in patients with normal renal function and those with renal failure did not differ significantly.

Vecuronium in renal failure

“…S In man, renal failure is associated with only small increases in the duration of neuromuscular block and recovery rate 6 as a result of statislically insignificant alterations in the pharmacokinetic behaviour of vecuronium in renal failure. 7 However, these observations are based upon small patient populations and there is no information of the potency, cumulative tendency, or reversibility of vecuronium in renal failure in man.…”

Interpleural or paravertebral block at thoracotomy?

“…1 whereby an epidural catheter is inserted into the chest at thoracotomy to provide access to the pleural cavity for postoperative infusion of bupivacaine. He suggests that this technique offers an alternative to more established postthoracotomy analgesic methods such as epidural, parenteral narcotics or intercostal nerve blocks.…”

Does vecuronium accumulate in the renal transplant patient?

“…Vecuronium has also been described as a suitable non-depolarizing agent for the clinically or anatomically anephric patient. ~.2 Fahey et al 2 showed no difference in onset or recovery time of vecuronium between normal and cadaver transplant patients. Another group t found no difference in duration of block or evidence of accumulation after multiple doses of vecuronium were administered to normal and anepbric patients.…”

“…They found no difference between the two groups in duration of action of either drug and no evidence of accumulation. Fahey et al 2 compared the pharmacokinetics of vecuronium in patients with and without renal failure and found no significant difference in duration or evidence of accumulation between the two groups. Other authors 3'4 have demonstrated that atracurium showed no evidence of accumulation or prolongation of effect in the renal failure patient.…”