Pharmacokinetics of TRIS (hydroxymethyl-)aminomethane in healthy subjects and in patients with metabolic acidosis

Summary

To investigate the pharmacokinetics of TRIS, an infusion of the buffer was given to 6 healthy volunteers (121 mg/kg=1 mmol/kg; pH 7.4) and to 20 patients suffering from metabolic acidosis (109–376 mg/kg; pH 10.9). The drug exhibited two-compartment characteristics in volunteers (t_0.5,β=5.6 h) and patients with intact renal function (t_0.5,β=16.3–45.6 h). The final volume of distribution (V_β) indicated uptake into tissues, but equilibration between body compartments was slow. Mainly unchanged TRIS was eliminated by the kidney; 82% of the administered dose was recovered from 24 h-urine of healthy subjects. In the patients a linear correlation between creatinine-clearance and TRIS-clearance was observed, the latter always being somewhat greater than the former. Only insignificant amounts of the drug were found in bile and gastric juice. In anuric patients the plasma concentration of TRIS declined monoexponentially, with a half-life between 10 and 58 h. Haemodialysis or haemofiltration did not influence this process. From the data it seems questionable whether cellular uptake of TRIS is an important factor in the therapy of intracellular acidosis, but the possibility of drug accumulation must be borne in mind if repeated doses are given to the same patient.