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Formate Kinetics in Folate Deficiency state in Young Swine
Author(s) -
Sokoro AbdulRazaq,
Lehotay Denis C,
Zello Gordon,
House James,
Alcorn Jane
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a247-b
Subject(s) - formate , chemistry , sodium formate , kinetics , metabolite , metabolism , biochemistry , organic chemistry , physics , quantum mechanics , catalysis
Objective: To investigate the effect of folate deficiency on formate kinetics during formate insult in young swine. Introduction: Formate is a toxic metabolite of MeOH. Detoxification of formate is through its metabolism to CO 2 and H 2 O. Folate is a required cofactor. Method: Twelve young pigs were pair‐matched and randomly divided into two groups on acquisition (~5 weeks). One group was made folate deficient (FFD) by elimination of folic acid from the diet, the other group (FFC) was supplement with folate. Four animals (31–38 kg) from each group were infused with 351mg/kg of sodium formate. The remaining 2 animals were injected with normal saline. Blood samples were collected before, and at 10, 20, 30, 45, 60, 90, 120, 180, 240 and 480 min post dose. Results: Formate accumulation in the FFD group was higher than the FFC group (AUC of 75830±44868 vs 34671±12952, respectively). Elimination was also slower in the FFD (clearance of 0.13±0.05 ml/min in FFC group compared to 0.27±0.14 and a slope of −0.009±0.003 vs −0.046±0.049, respectively). Half‐life was 2.9 times higher in FFD group than in FFC group (86±29 min vs 30±22). A first order kinetics was observed in the FFC and zero order kinetics for the FFD. Conclusion: Adequate folate state is important in faster elimination of formate. A deficiency state alters formate pharmcokinetics, increasing risk of formate toxicity.