Chronic administration does not alter the accumulation of L-dopa into muscle.
Rats were treated for 12 months with L-dopa (191.4-210.4 mg/kg/day) plus carbidopa (23.9-26.2 mg/kg/day), or carbidopa (24.4-26.3 mg/kg/day) alone. Four days after drug withdrawal, animals received an acute challenge with either L-dopa (50 mg/kg p.o.) alone or following acute carbidopa (25 mg/kg i.p.) pretreatment, and the uptake and metabolism of L-dopa in muscle was studied. Following the acute bolus challenge, plasma levels of L-dopa peaked between 0.5 and 3 h after L-dopa alone and between 1.5 and 2 h after L-dopa plus carbidopa. Peak levels in muscle were observed between 1.5 and 4 h after L-dopa administration, and this accumulation was enhanced by the acute pretreatment with carbidopa. Chronic administration of L-dopa plus carbidopa or carbidopa alone for 12 months had no effect on the accumulation of L-dopa into muscle following the acute challenge with L-dopa alone or after carbidopa pretreatment. 3-O-Methyldopa, dopamine, DOPAC, and HVA levels were elevated in both plasma and muscle following acute oral challenge with L-dopa or L-dopa plus carbidopa. Levels of these metabolites were unaffected by chronic administration of L-dopa plus carbidopa or carbidopa alone. In conclusion, chronic administration of L-dopa plus carbidopa did not alter the accumulation of L-dopa into muscle following an acute oral challenge with the drug, with or without carbidopa pretreatment.
Rose
S
S
Parkinson's Disease Society Experimental Research Laboratories, King's College, London, U.K.
Jenner
P
P
Marsden
C D
CD
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D002230:Carbidopa / Q000008:administration & dosage / Q000493:pharmacokinetics; D004298:Dopamine / Q000378:metabolism; D004359:Drug Therapy, Combination; D006719:Homovanillic Acid / Q000378:metabolism; D007980:Levodopa / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D008134:Long-Term Care; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; C035420:levodopa methyl ester; D002230:Carbidopa; D004298:Dopamine; D006719:Homovanillic Acid