Summary
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 μg VS 18.28±4.58 μg) 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 μg VS 6.49±0.84 μg), 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 μg VS 182.6±78.5 μg 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.
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Mallein, R., François, B., Rondelet, J. et al. Pharmacokinetic study of Pyridinol carbamate in Chronic Renal Insufficiency. European Journal of Drug Metabolism and Pharmacokinetics 9, 141–148 (1984). https://doi.org/10.1007/BF03189617
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DOI: https://doi.org/10.1007/BF03189617