Formate pharmacokinetics during formate administration in folate-deficient young swine

The objective of the study was to investigate the effect of folate deficiency on formate pharmacokinetics during formate administration in folate-deficient young swine. Methanol is a one of the congeners found in alcoholic beverages. Methanol toxicity is mediated through formic acid and thus plays a significant role in the pathophysiology of alcoholism. Folate is a required cofactor in the metabolism of formate to CO2 and H2O. We investigate the effect of folate deficiency on the pharmacokinetics of formate. Twelve young pigs were pair-matched and randomly placed into 2 groups on acquisition (∼5 weeks). One group was made folate deficient (FFD) by feeding with a folic acid–deficient diet; the other group (FFC) was fed a diet supplemented with folate. Four animals (31-38 kg) from each group were infused (intravenous) with 351 mg/kg of sodium formate. The remaining 2 animals were infused with isotonic sodium chloride solution. Blood samples were collected before and at 10, 20, 30, 45, 60, 90, 120, 180, 240, and 480 minutes post dose and analyzed for formate levels by gas chromatography. Pharmacokinetic parameters were estimated using a noncompartmental approach. Formate (mean ± SE) accumulation was higher in the FFD group than the FFC group (AUC0-∞ of 72.37 ± 8.29 vs 30.08 ± 2.58 g min/L, respectively). Elimination was also slower in the FFD group (FFD systemic clearance = 0.12 ± 0.01 L/min compared with FFC systemic clearance = 0.27 ± 0.02 L/min). Half-life of elimination was 2.5 times longer in FFD group (113 ± 1 minute) than in FFC group (45 ± 6 minutes). Folate deficiency had no influence on the volume of distribution of formate (18.84 ± 1.05 L in FFD vs 17.21 ± 1.35 L in FFC). Adequate folate status is important in the elimination of formate. A folate-deficiency state results in a reduction in formate elimination kinetics, which may increase the risk of formate toxicity.