Clinical significance of the relationship between O-methyldopa levels and levodopa intake.

A recent clinical trial of controlled-release carbidopa/levodopa preparation afforded us the opportunity to examine the effects of chronically increasing circulating 3-O-methyldopa (OMD) levels on the clinical response to levodopa. In patients taking standard Sinemet, both mean plasma OMD levels and the area under the plasma concentration-versus-time curve (AUC) obtained during 8-hour periods of blood sampling correlated highly with the total daily intake of levodopa. In patients taking the controlled-release formulation, the mean daily intake of levodopa was doubled. This, in turn, led to a doubling of the mean OMD level and its AUC, whereas the AUC for levodopa was unchanged. Despite the increase in circulating OMD there was no reduction in mobility in either the "on" or "off" conditions. Thus, doubling plasma OMD levels did not seem to interfere with brain uptake of levodopa sufficiently to cause a deterioration in its therapeutic efficacy in these patients.