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Abstract

This study established the fasting plasma and urine profiles of vitamin B6 in cirrhotics and assessed the response to an oral dose of pyridoxine. High-performance liquid chromatography was used to measure all vitameric coenzymatic and degradatory forms. In 31 patients with cirrhosis and 15 healthy controls, fasting plasma and 24-hr urine collection showed: plasma pyridoxal-5′-phosphate, the biologically active form, was significantly (p<0.001) reduced in cirrhotics (mean ± S.D.: 5.7 ± 3.2 ng per ml) compared to normals (14.2 ± 7.5 ng per ml); plasma pyridoxal was detected in more cirrhotics (48%) than normals (28%); pyridoxic acid, the end catabolite, was significantly (p<0.05) lower in plasma of cirrhotics compared to normals, but 24-hr urine excretion was not different. Administration of 25 mg of pyridoxine to 7 cirrhotics and 5 normals showed the following plasma changes: (i) pyridoxine rapidly peaked at 30 min and was totally cleared from plasma by 3 hr; (ii) plasma pyridoxal and pyridoxic acid increased in parallel up to 40-fold over baseline by 1 to 2 hr and rapidly fell toward baseline by 8 hr, and (iii) plasma pyridoxal-5′-phosphate, in contrast, increased significantly (p<0.05) from baseline by 60 min and was maintained above normal for 24 hr. The area under the plasma concentration vs. time curve (AUC) for pyridoxal-5′-phosphate was significantly (p<0.05) less for the cirrhotics than normals and showed a significant negative correlation to hepatocyte function and blood flow. This suggests that it is most difficult to replete plasma pyridoxal-5′-phosphate in those cirrhotics with best preservation of liver function and flow. In contrast, the plasma pyridoxal AUC is significantly (p<0.025) greater in the cirrhotics after the pyridoxine load. Plasma pyridoxic acid AUC and urine pyridoxic acid excretion (27% of load per 24 hr) are not significantly different for the two groups. The data are consistent with normal pyridoxal-5′-phosphate synthesis since plasma pyridoxal-5′-phosphate levels are maintained within the normal range by a single 25 mg oral dose of pyridoxine. However, the smaller AUC for pyridoxal-5′-phosphate in cirrhotics compared to normals, combined with the increased pyridoxal AUC, shows increased bydrolysis to pyridoxal. This is not excreted as pyridoxic acid and suggests that pyridoxal may be entering intracellular sites.