Sinemet‐ferrous sulphate interaction in patients with Parkinson's disease.

Abstract

1. This study examined the effects of administering ferrous sulphate 325 mg with Sinemet (100/25 tablet) on levodopa and carbidopa bioavailability and on signs of Parkinson's disease in nine patients. 2. Ferrous sulphate ingestion with Sinemet resulted in a decrease in levodopa area under the curve (AUC) of 30% (P less than 0.01) and a greater than 75% decrease in carbidopa AUC. Despite a strong relationship between reductions in levodopa AUC and reductions in Sinemet efficacy (r = 0.83, P less than 0.01), the average reduction in Sinemet's efficacy associated with ferrous sulphate did not achieve statistical significance (P = 0.055). 3. Chemical studies indicate that iron forms chemical complexes with carbidopa in a similar manner to levodopa and is a likely mechanism for the drug interactions. 4. AUC when a Sinemet tablet is taken concurrently with a ferrous sulphate tablet appears to be clinically significant in some but not all patients. The clinical significance of repeated ingestion of ferrous sulphate with Sinemet requires further studies.

Pharmacokinetic characteristics of agents applied in the treatment of Parkinson’s disease

“…L-dopa displays drug interactions with iron and isoniazid. Both drugs decrease the effect of L-dopa [3,4]. Dopamine receptor agonists are metabolized by CYP enzymes.…”

Drug-drug interactions with levodopa modulating treatment responses in Parkinson's disease

“…For all these reasons any reduction of carbidopa is expected to impair clinical responses to levodopa. This effect is a direct physicochemical interaction in the gut lumen and is largest in those patients with the highest levodopa bioavailabilities [6].…”

“…Even when administered as ferrous (Fe ++ ) sulphate both rate and extent of absorption are decreased by 30-50 % [5,6] immediately translating into changes in efficacy in many patients [6]. In addition, when carbidopa was co-administered, which has also a catechol structure, iron complexes with carbidopa were formed and the compound was partly inactivated with ferrous sulphate reducing its bioavailability by > 75 % [6]. Such reductions are critical because with current daily doses AADC activity is not completely blocked in all patients [13].…”

Management of Constipation in Patients With Parkinson Disease

“…23,24 It is known that protein intake interferes with levadopa therapy. There are combination products available that contain iron and stool softeners.…”