A comparison of the effects of controlled-release levodopa (Madopar CR) with conventional levodopa in late Parkinson's disease.

Abstract

In this multicentre study a controlledrelease formulation of levodopa and the decarboxylase inhibitor benserazide (Madopar CR) was evaluated in patients with Parkinson's disease exhibiting doserelated fluctuations in motor performance in response to conventional levodopa preparations. The effect of Madopar CR, with or without conventional levodopa/benserazide, on the proportion of time spent "on", "off" or "intermediate" was compared with that ofprevious conventional levodopa/decarboxylase inhibitor therapy. Evaluation of the two periods of optimum therapy was based on both patient diary data and investigator opinion. Forty seven patients completed the study but full patient diaries were available for only 37. The mean optimum total daily dosage of conventional Madopar was 820 mg taken in a mean of 6-4 doses, compared with a mean optimum daily dosage of combined Madopar CR and conventional Madopar of 1088 mg, taken in a mean of 5 2 doses. Conventional Madopar was taken in addition to Madopar CR in all but eight patients. Madopar CR was felt to be advantageous in 83% and disadvantageous in 11% of patients completing the study. Considering the 37 patients for whom diary data were available, Madopar CR therapy resulted in an increase in the mean time spent "on" (p = 0-016) and a decrease in the mean time spent "off" (p = 0-029) compared with conventional Madopar alone. Individually 25 out of 37 had an increase in "on" time and 19 out of 37 experienced a decrease in "off" time. Thus Madopar CR was found to be beneficial in a significant proportion of patients experiencing fluctuations in response to conventional levodopa.

Levodopa in the Treatment of Parkinson's Disease: Current Status and New Developments

“…During the late 1980 s, controlled-release (CR) levodopa formulations were developed with the aim of improving levodopa delivery to the brain, and such CR tablets have been commercially available since 1991. CR compounds consist of levodopa, in combination with either carbidopa or benserazide, embedded in a matrix designed to delay the release of the active ingredients, resulting in delayed absorption and more sustained plasma levodopa levels, as compared with regular levodopa [15,16]. The bioavailability of CR-levodopa formulations is, however, somewhat unpredictable and generally lower than that with conventional levodopa, thereby necessitating a ∼30% increase in dose [17][18][19].…”

“…As mentioned above, although CR-levodopa formulations were developed to provide more consistent delivery of levodopa, results from clinical trials in patients with motor fluctuations have demonstrated conflicting results compared with immediate-release levodopa formulations [15,16,[20][21][22]93]. While these levodopa formulations may benefit certain patients, irregular gastric absorption and competition with amino acids make achieving a predictable drug response difficult.…”

The distorted body: The perception of the relative proportions of the body is preserved in Parkinson’s disease

“…Moreover, the area of cortical alteration correlates with the duration of motor disruption (Liepert et al, 1995 ). Antiparkinsonian medication reduces motor fluctuations (DeMaagd & Philip, 2015 ; MacMahon et al, 1990 ), therefore most individuals with PD typically do not experience severely reduced motoric abilities for prolonged periods (Nutt et al, 1984 ). Specifically, here 50% of participants reported they had no on/off time, 30% spent ≤ 25% of their waking hours in an ‘off’ state, 14% spent 26–50% of their waking hours in an ‘off’ state, and 6% spent 51–75% of waking hours in an ‘off’ state.…”

How far can I reach? The perception of upper body action capabilities in Parkinson’s disease

“…Furthermore, whilst individuals can seemingly fluctuate from an “on” to an “off” time throughout the course of the day (Lang et al, 1982 ; Stacy et al, 2005 ), the stable maintenance of blood plasma levodopa concentration provided by medication reduces swings in motor performance (MacMahon et al, 1990 ), ensuring that patients spend more time in an “on” time throughout the course of a day. Within the sample tested here, 40% of patients reported they had no on/off time, 45% spent ≤25% of their waking hours in an “off” state, and the remaining 15% spent 26%–50% of their waking hours in an “off” state.…”