What is the rationale for combining levodopa with carbidopa

PERIPHERAL DECARBOXYLASE INHIBITORS Carbidopa and benserazide are extracerebral dopa decarboxylase inhibitors; they do not penetrate blood-brain barrier and do not inhibit conversion of levodopa to DA in the brain. Administered along with levodopa, they increase its t 1/2 in the periphery and make more of it available to cross blood-brain barrier and reach its site of action. Benefits of the combination are-- 1. The plasma t 1/2 of levodopa is prolonged and its dose is reduced to approximately 1/4th. 2. Systemic concentration of DA is reduced, nausea and vomiting are not prominent therapeutic doses of levodopa can be attained quickly. 3. Cardiac complications are minimized. 4. Pyridoxine reversal of levodopa effect does not occur. 5. 'On-off' effect is minimized since cerebral DA levels are more sustained. 6. Degree of improvement may be higher; some , patients not responding adequately to levodopa alone, also improve. Ref:- kd tripathi; pg num:-429,430