Oral solution of levodopa ethylester for treatment of response fluctuations in patients with advanced Parkinson's disease.
Levodopa ethylester (LDEE), a highly soluble prodrug of levodopa, may overcome the impaired absorption of regular levodopa, due mainly to a combination of levodopa's poor solubility and delayed gastric emptying. We conducted a double-blind, levodopa-controlled, multicenter study of oral LDEE solution compared with standard levodopa-carbidopa (LD-CD) tablets. Sixty-two patients with Parkinson's disease who had "delayed on" and "no-on" subtypes of response fluctuations were randomly assigned for treatment with LDEE-CD or LD-CD 250/25 mg for 4 weeks (phase A). Only the first morning and first post-lunch dose of LD were replaced. This was followed by a 2-week extension with a supplementation of carbidopa (25 mg) to each replaced dose (phase B). Patients filled home diaries 2 weeks before and during the trial period in which times of turning on and off for the two doses were reported. In phase A, mean latency to turning on was reduced by 21% (morning dose) and 17% (post-lunch dose) in the LDEE-CD group. Percentage of no-on episodes after the post-lunch dose was decreased by 21% in the LDEE-CD group but increased by 36% in the LD-CD group (P < 0.01). In phase B, LDEE-CD decreased latencies to on after the morning and post-lunch doses and no-on episodes after the post-lunch dose. The beneficial effects of LDEE were supported by the pharmacokinetic data. Results indicate that LDEE solution is beneficial in ameliorating delayed on and no-on response fluctuations. This effect of LDEE is due to more rapid levodopa absorption.
Djaldetti
Ruth
R
Department of Neurology, Rabin Medical Center, Petah Tiqva, Israel.
Inzelberg
Rivkah
R
Giladi
Nir
N
Korczyn
Amos D
AD
Peretz-Aharon
Yehudit
Y
Rabey
Martin J
MJ
Herishano
Yuval
Y
Honigman
Silvia
S
Badarny
Sami
S
Melamed
Eldad
E
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001682:Biological Availability; D002230:Carbidopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D004338:Drug Combinations; C009265:carbidopa, levodopa drug combination; C454359:levodopa ethylester; D007980:Levodopa; D002230:Carbidopa