Concentrations of D-glucaric acid in human urine after repeated administration of pyrithioxine.
The urinary excretion of D-glucaric acid in 16 healthy male volunteers, 24 to 66 years of age, was 44 +/- 3 mumol/24 h (25 +/- 2 mumol D-glucaric acid/g creatinine/24 h). Six healthy female volunteers aged 25 to 60 years excreted 42 +/- 5 mumol D-glucaric acid/24 h (30 +/- 3 mumol D-glucaric acid/g creatinine/24 h) in the urine. (The values given are means +/- s.e.m.) In 3 male subjects, daily i.v. infusion of 5 mg pyrithioxine in 3 ml physiol. saline/kg body weight on 5 successive days produced a slight increase in the daily renal excretion of D-glucaric acid during the 5-day period. The increase was reversible during the next few days. Oral doses of 200 mg pyrithioxine, given three times daily over a period of 4 weeks to 5 female subjects caused a slight increase in the renal excretion of D-glucaric acid/24 h. In the course of the following week, there was a return to baseline levels. The pyrithioxine-associated increase in urinary D-glucaric acid is attributed to its enhanced metabolic formation in the body and indirectly reflects a weak inductive action of pyrithioxine on the hepatic microsomal enzyme system in man. With the evidence on hand, this effect, though slight in extent, would appear to predict no risk of a pharmacokinetic interaction between pyrithioxine and other drugs.
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D005260:Female; D005937:Glucaric Acid / Q000378:metabolism / Q000652:urine*; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects; D008875:Middle Aged; D011725:Pyridines / Q000494:pharmacology*; D011746:Pyrithioxin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D013400:Sugar Acids / Q000652:urine*; D013997:Time Factors
D011725:Pyridines; D013400:Sugar Acids; D011746:Pyrithioxin; D005937:Glucaric Acid