Pharmacokinetics of 1R-cis 1'R-cis atracurium besylate (51W89) and plasma laudanosine concentrations in health and chronic renal failure

Abstract

To ascertain the effects of chronic renal failure on the pharmacokinetics of 1R-cis 1'R-cis atracurium besylate (a stereoisomer, designated 51W89), we gave a bolus dose of 0.1 mg kg-1 (2 x ED95) to 17 patients with end-stage renal failure and to 15 patients with normal renal function undergoing elective surgery. All patients received thiopentone, fentanyl and midazolam i.v. and 70% nitrous oxide in oxygen. Blood samples were obtained over 8 h and plasma analysed for 51W89 and laudanosine concentration, using high pressure liquid chromatography. A two-compartment model was fitted to the 51W89 plasma concentration data using the NONMEM program, to estimate pharmacokinetic variables and to determine the influence of renal failure, age, weight and sex. Clearance of 51W89 was found to be reduced by 13% in renal failure. The typical value of T1/2 beta was 4.2 min longer in renal failure than in the healthy patients (34.2 vs 30.0 min, P < 0.005). In the healthy patients, clearance of 51W89 was greater in males, but it decreased with increasing age by approximately 1.5 ml min-1 yr-1. Mean plasma laudanosine concentrations were significantly higher in the renal failure group; nevertheless, they were approximately one-tenth of those reported after atracurium.

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement

“…Noticeable differences occur in terms of potency and cardiovascular adverse effects. Cisatracurium is four times as potent as atracurium and does not produce any cardiovascular effects, whereas atracurium can cause hypotension and tachycardia (97)(98)(99).…”

Cisatracurium bei Patienten mit eingeschränkter Nierenfunktion

“…Nach unserer Kenntnis liegt bislang nur eine geringe Anzahl von Arbeiten vor, die sich mit der Anwendung von Cisatracurium bei Patienten mit eingeschränkter Nierenfunktion befassen [3,9].…”

“…In einer vergleichenden Untersuchung von gesunden Patienten und Patienten mit eingeschränkter Nierenfunktion fanden Eastwood und Mitarbeiter eine signifikant verlängerte Plasmaeliminationshalbwertzeit (30,0 ± 1,2 min vs. 34,2 ± 1,2 min; p < 0,005) und eine um 13% reduzierte Plasmaclearance (293 ± 9,9 ml/min vs. 254 ± 12,2 ml/min). Die mittlere Laudanosinkonzentration, dem Metaboliten, der zum Teil renal aber auch hepatisch eliminiert wird, war zwar bei Patienten mit eingeschränkter Nierenfunktion signifikant erhöht, sie erlangte jedoch keine klinische Relevanz [9]. Vergleicht man diese Ergebnisse mit Angaben über die Mutonsbedingungen lagen nach 2-3 min bei allen Patienten vor.…”

Pharmacodynamics of cisatracurium in the intensive care unit: an observational study

“…Impaired renal or liver function has little influence on the pharmacokinetics of this drug [2,3]. The volume of distribution of cisatracurium is limited to the extracellular fluid (144 mL.kg -1 ), total plasma clearance is approximately 5.3 mL.min -1 .kg -1 , and the elimination half life is between 22 and 30 minutes [4,5]. …”