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UGT1A6 genotype-related pharmacokinetics of deferiprone (L1) in healthy volunteers

, : UGT1A6 genotype-related pharmacokinetics of deferiprone (L1) in healthy volunteers. British Journal of Clinical Pharmacology 65(6): 908-916

AIMSTo examine the effects of UGT1A6 polymorphisms on the pharmacokinetics of deferiprone in healthy volunteers.METHODSTwenty-two healthy volunteers were enrolled and grouped according to UGT1A6 genotype. After an overnight fast, the subjects received a single oral dose of 25mg kg(-1) deferiprone. Blood samples were collected at 0, 15, 30, 45, 60, 90, 120, 180, 240, 300 and 360 min after dosing. Urine output was collected at 0, 0-2, 2-4, 4-8, 8-12 and 12-24 h. Deferiprone (L1) and deferiprone-glucuronide (L1G) concentrations in serum and urine were determined using a validated high-performance liquid chromatography method. UGT1A6 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis.RESULTSNo statistically significant differences in any pharmacokinetic parameters of either deferiprone or deferiprone-glucuronide among the genotype groups were noted. Likewise, there were no statistically significant differences in 24-h urinary deferiprone and deferiprone-glucuronide excretion among the genotype groups. Significant differences between men and women were found in AUC(0-infinity), V-d/F, and CL/F of deferiprone. Gender differences in 24-h urinary deferiprone and its metabolite excretion, however, failed to reach statistical significance. The Vd/F of deferiprone was found to correlate significantly with serum ferritin (r(s) = 0.665; P = 0.001).CONCLUSIONThe studied single nucleotide polymorphisms in UGT1A6 do not appear to exert statistically significant effects on the single-dose pharmacokinetics of deferiprone. Gender appears to influence the serum pharmacokinetics of deferiprone, but not urinary excretion of deferiprone and its metabolite. Body iron stores may have an influence on the extent of extravascular deferiprone distribution.


PMID: 18318774

DOI: 10.1111/j.1365-2125.2008.03103.x

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