THE PHARMACOKINETICS OF AMINOGUANIDINE IN END-STAGE RENAL-DISEASE PATIENTS ON HEMODIALYSIS

Aminoguanidine is an investigational agent that may slow or prevent ma ny diabetes-related complications, Since the elimination of aminoguani dine is dependent on renal function, its pharmacokinetics was investig ated in eight chronic renal failure patients maintained on hemodialysi s, Each patient received 300 mg of aminoguanidine hydrochloride during both an interdialytic and an intradialytic period, During the interdi alytic period, the maximum aminoguanidine concentration (Cmax) and tim e to reach Cmax was 4.5 mu g/mL and 1.5 hours, respectively, The termi nal elimination half-life in these patients was prolonged (37.9 hours) , The renal clearance was 2.1 mL/min. Only 8.7% of the administered do se was recovered unchanged in the urine, which is markedly reduced fro m what is recovered in urine in subjects with normal renal function, T here was a positive correlation between the renal clearance of aminogu anidine and the patients' residual renal function (P < 0.05). During h emodialysis, the half-life of aminoguanidine was shortened to 3.9 hour s, The hemodialysis clearance of aminoguanidine was 203.6 mL/min, Afte r cessation of hemodialysis, a significant rebound in plasma aminoguan idine concentrations (mean, 39%) was observed, Thus, the dose of amino guanidine hydrochloride will need to be significantly reduced in patie nts with end-stage renal disease, Given the interdialytic and intradia lytic pharmacokinetics of aminoguanidine, three times weekly dosing af ter each hemodialysis session is suggested. (C) 1995 by the National K idney Foundation, Inc.