PHARMACOKINETICS OF 1R-CIS 1'R-CIS ATRACURIUM BESYLATE (51W89) AND PLASMA LAUDANOSINE CONCENTRATIONS IN HEALTH AND CHRONIC-RENAL-FAILURE

To ascertain the effects of chronic renal failure on the pharmacokinet ics of 1 R-cis 1'R-cis atracurium besylate (a stereoisomer, designated 51W89), we gave a bolus dose of 0.1 mg kg(-1) (2 x ED(95)) to 17 pati ents with end-stage renal failure and to 15 patients with normal venal function undergoing elective surgery. All patients received thiopento ne, fentanyl and midazolam i.v. and 70% nitrous oxide in oxygen. Blood samples were obtained over 8 h and plasma analysed for 51W89 and laud anosine concentration, using high pressure liquid chromatography. A tw o-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. Cleara nce of 51W89 was found to be reduced by 13% in renal failure. The typi cal value of T-1/2(beta) was 4.2 min longer in renal failure than in t he healthy patients (34.2 vs 30.0 min, P<0.005). In the healthy patien ts, clearance of 51W89 was greater in males, but it decreased with inc reasing age by approximately 1.5 mi min(-1) yr(-1). Mean plasma laudan osine concentrations were significantly higher in the renal failure gr oup; nevertheless, they were approximately one-tenth of those reported after atracurium.