Sex differences in the pharmacokinetics of levodopa and carbidopa in patients with Parkinson's disease

Abstract

Introduction

Levodopa pharmacokinetics exhibit substantial interindividual variability. Sex has been recognized as a contributing factor, with female patients frequently showing higher plasma levodopa concentrations than male patients. However, data on the pharmacokinetics of aromatic L‒amino acid decarboxylase (AADC) inhibitors such as carbidopa, which are co‒administered with levodopa, remain limited. This study aimed to evaluate the impact of sex and other variables on the pharmacokinetics of both levodopa and carbidopa in patients with Parkinson's disease (PD).

Methods

We conducted a retrospective analysis of patients with PD who underwent pharmacokinetic evaluation following the administration of an oral levodopa/carbidopa formulation in the fasting state. Pharmacokinetic parameters, including maximum plasma concentration, time to reach the maximum concentration, and the area under the plasma concentration‒time curve (AUC), were calculated. Multiple regression analysis was performed to identify factors associated with AUC.

Results

A total of 42 patients (21 males, 21 females; mean age 72.88 ± 7.51 years) were included. The AUC of levodopa was significantly higher in female patients than in male patients (p = 0.017), while no significant sex‒related differences were observed in the pharmacokinetics of carbidopa. Multiple regression analysis estimated that female sex was associated with a 21.9 % increase in levodopa AUC compared to male sex.

Conclusions

Our findings suggest that sex significantly influences levodopa pharmacokinetics but has little effect on carbidopa. Further studies are warranted to elucidate the mechanisms underlying this sex difference and to determine whether similar effects occur with other AADC inhibitors.