Key words : Zonisamide, Metabolism, Plasma, Erythrocytes, Preputial gland, Urine, Bile, Rat, Dog, Monkey Metabolism of ["Clzonisamide in rats, dogs and monkeys Katashi MATSUMOTO, Koji YOSHIDA, Toshihiko Fu.ni, Hideo FURUKAWA, Hisashi MIYAZAKI and Masahisa HASHIMOTO Research Laboratories, Dainippon Pharmaceutical Co. Ltd., Enoki 33-94, Suita, Osaka 564, Japan
Fig. 1. Structure of [methyl-14c]zonisamide
Fig. 2. Typical TLC-radiochromatograms of metabolites in plasma (a), erythrocytes (b) and preputial gland (c) after oral administration of [14C]zonisamide in rats (20 mg/kg) Solvent system : chloroform/methanol/28 % am monia water (50/20/1) O : origin, F : solvent front. Closed circles indi cate the position of authentic references after development. UD : unchanged zonisamide, C carboxylic acid.
Fig. 3. Typical TLC-radiochromatograms of urinary metabolites after oral administra tion of [14C] zonisamide in animals (20 mg/kg) A : acetylated-zonisamide See also the legend of Fig. 2. Table I. Composition of urinary metabolites after administration of [14C]zonisamide in some animal species Values are means of n animals (±S.E.). Empty columns indicate no determinations. : not detected n : Number of animals UD : Zonisamide, MI : Zonisamide glucuronide, MIT : Conjugate of N-O cleaved com pound, Rat MIT is the fraction containing unknown metabolite(s). MIII : Acetylated-zonisamide, MTV Glucuronide of hydroxylated-zonisamide, MV : Carboxylic acid. Dog MV is a glucuronide. * : Previously idertified by TLC/MS in rat urine'). ** : p<0.01, compared with single administration
Fig. 4. A typical TLC-radiochromatogram of bile metabolites after oral administra tion of [14C]zonisamide in rat (20mg/ kg). See also the legend of Fig. 2. Fig. 5. Metabolic pathways of zonisamide in animals
Fig. 6. A typical TLC radiochromatogram profile of the extract from dog urine treated with Q-glucuronidase after pretreatment with ethyl acetate (a) and mass spectra of metabolite PI, PII and Pill (b) N : N-O cleaved compound See also the legend of Fig. 2.
Fig. 7. A typical TLC-radiochromatogram profile of intact monkey urine (a) and mass spectra of metabolite P'I and P'II (b). See also the legend of Fig. 2 and 3.
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