Kinetics of Absorption and Excretion of Levodopa in Dogs

Abstract The rate and extent of levodopa absorption and excretion following intravenous and oral administration of 2− 14 Clevodopa to acute and chronically treated dogs were investigated. Plasma levels of intact levodopa following the intravenous administration declined rapidly during the first 4-6 hr. The elimination-rate constant of intact levodopa from the plasma ranged between 0.73 and 0.99 hr. −1 , which corresponds to a half-life of approximately 40-60 min. The elimination-rate constant of total plasma 14 C ranged between 0.007 and 0.085 hr. −1 , which corresponds to a half-life of 8-9 hr., indicating that the total 14 C was eliminated at one-tenth the rate of intact levodopa. Peak plasma levels of intact levodopa and of total plasma 14 C following oral administration were attained 25-30 min. after dosing. Approximately 70-75% of the intravenous and 57-70% of the oral radioactive doses were excreted in urine over a 72-hr. period. Levodopa and dopamine accounted for a very small percentage of the radioactivity in the urine. Approximately 3.0-7.0% of the intravenous or oral radioactive dose was excreted in the feces. The efficiency of absorption of total radioactivity was calculated to range between 83.0 and 92.0%. Analysis of the ratio of intact levodopa levels to total 14 C levels indicated that only 22.0-30.0% of the administered dose reached the general circulation as intact levodopa, suggesting that the remainder of the absorbed dose, approximately 60.0%, is biotransformed in the gastrointestinal tract prior to absorption and/or in the liver during its "first passage" to the general circulation.