Dosage form design for improvement of bioavailability of levodopa IV: Possible causes of low bioavailability of oral levodopa in dogs

✍ Scribed by Kunihiro Sasahara; Takashi Nitanai; Taeko Habara; Toshimasa Kojima; Yukinori Kawahara; Tadashi Morioka; Eiichi Nakajima

• Publisher: John Wiley and Sons
• Year: 1981
• Tongue: English
• Weight: 476 KB
• Volume: 70
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600700705

✦ Synopsis

Several potential mechanisms for reduced levodopa bioavailability following oral administration to dogs and humans were investigated by studying the influence of the administration route on plasma levodopa levels after intravenous, hepatoportal, and duodenal administrations to dogs. The observed average areas under the plasma concentration-time curves (AUC) of levodopa following hepatoportal injection and intravenous injection were virtually identical; but following duodenal administration a decrease in the AUC of levodopa was observed with a concomitant increase in the AUC of total dopamine. The possible involvement of intestinal microorganisms in levodopa metabolism was explored in dogs that had been administered a combination of paromomycin and kanamycin to reduce intestinal microflora. Similar patterns of plasma level profiles and urinary excretion were observed between control and treated dogs. As measured by the release of [14C]carbon dioxide from [14C]levodopa, the distribution of levodopa decarboxylase enzyme activity in various parts of the intestine was studied in homogenates prepared from isolated intestinal segments of the duodenum and upper, middle, and lower parts of the jejunum and ileum. The jejunum showed the highest decarboxylase activity followed by the ileum and duodenum. These data indicate that the reduced bioavailability of orally administered levodopa occurs as a result of metabolism by levodopa decarboxylase enzyme in the gut wall.

Keyphrases Levodopa-bioavailability, effect of administration route, metabolism, intestinal microorganisms, levodopa decarboxylase Bioavailability,-levodopa, effect of administration route Antiparkinsonian agents-levodopa, effect of administration route on bioavailability 3 This benzethonium chloride solution waa prepared from a 10-fold dilution of Hyamine, Sankyo Co.