Chapter 17 Biotransformation and excretion: Quantitative studies of tissue metabolism

This chapter discusses two particular pharmacologic problems in Parkinson disease, which are investigated with stable isotope labeled levodopa. It presents the rational for applying stable isotope technology over other existing pharmacologic methods. Levodopa infusion studies examining response to increasing infusion rates indicate that once clinical improvement is noted in advanced Parkinson disease, the magnitude of that response cannot be improved by simply increasing the levodopa infusion rate. The peripheral decarboxylation of levodopa to dopamine after sole levodopa administration is responsible for significant side effects, which include nausea, vomiting, and potentially fatal cardiac arrhythmias. Carbidopa blocks this peripheral conversion by acting as a competitive inhibitor of dopa decarboxylase. As it does not cross the blood-brain barrier, there is no interference with central decarboxylation of levodopa to dopamine. Thus, the effect of carbidopa when coadministered with levodopa is to substantially reduce systemic side effects of levodopa and make more systemic levodopa available for central conversion to dopamine.