Pharmacokinetic study of pyridinol carbamate in chronic renal insufficiency.

The pharmacokinetics of Pyridinol carbamate (PDC) were studied over a 48 hour period in 14 patients with Chronic Renal Failure (C.R.F.) and in 10 normal controls. Following a single oral dose of 1 gm of PDC, the serum was assayed for PDC and M1 (monodemethylated PDC, the 1st metabolite) and the urine for PDC: M1, and M2 (second metabolite). The C max of PDC was found to be increased in the patients with C.R.F. when compared with the controls (21.8 +/- 5.26 micrograms VS 18.28 +/- 4.58 micrograms) but the half-life was unchanged (6.56 +/- 3.93 h VS 5.86 +/- 1.5 h). There was no difference between the C max of M1 of the patients and that of the controls (7.04 +/- 1.5 micrograms VS 6.49 +/- 0.84 micrograms), but there was an increase in the half-life (21.28 +/- 15.86 h VS 11.78 +/- 5.86) and of the area under curve (319.8 +/- 170.8 micrograms VS 182.6 +/- 78.5 micrograms ml-1 h). The overall excretion of PDC, M2 and particularly of M1 was found to be decreased and a higher concentration of PDC was noted in the urine of C.R.F. group. A correlation between the concentration of M2 and the severity of C.R.F. was observed, in that lower concentration or the absence of M2 in the 1st 6 hour urine sample appeared to be directly related to the severity of renal failure. Current evidence suggests that the N-demethylation of PDC remains normal in CRF and that there is enhanced transformation of M1 to ;M2.