The effects of carbidopa dose and time and route of administration on systemic L-dopa levels in rats.
The effects of carbidopa dose and time and route of administration on systemic plasma levels of parenterally and nonparenterally administered L-dopa were examined in rats. Intravenous coadministration of L-dopa + carbidopa resulted in significant (P less than 0.05) carbidopa-dependent increases in both the area under the plasma L-dopa concentration versus time profile (AUC; +27%) and the plasma L-dopa half-life (t1/2; +35%). Simultaneous duodenal or rectal carbidopa administration did not alter the L-dopa i.v. pharmacokinetic profile. Carbidopa pretreatment significantly increased the i.v. L-dopa AUC (+38 and +82% for i.v. and duodenal pretreatments, respectively) compared to simultaneous administration. Both i.v. and duodenal carbidopa increased duodenal L-dopa AUC to a similar extent (+282 and +239% for i.v. and duodenal administration, respectively). Rectal studies indicated poor absorption of both L-dopa and carbidopa, with no demonstrable effect on plasma L-dopa. The results indicate that the timing and route of carbidopa and L-dopa administration are important in determining the extent of i.v. or duodenal L-dopa systemic availability. The rat model affords results similar to those reported in human studies and may be useful for more extensive evaluation of L-dopa and carbidopa interactions.
Leppert
P S
PS
INTERx Research Corporation, Merck Sharp & Dohme Research Laboratories, Lawrence, Kansas 66046.
Cortese
M
M
Fix
J A
JA
D000818:Animals; D002230:Carbidopa / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D007275:Injections, Intravenous; D007441:Intubation, Gastrointestinal; D007980:Levodopa / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D007980:Levodopa; D002230:Carbidopa