Female, aging, difference formulations of DCI, or lower body weight increases AUC4hr of levodopa in patients with Parkinson's disease

Abstract

IntroductionThere is considerable intra- and inter-individual variability in the pharmacokinetics (PK) of levodopa after oral administration. Inter-individual variability in levodopa PK has also been demonstrated in fasting single-dose studies. We examined the factors that affect levodopa PK in patients with Parkinson's disease (PD) and quantified the intensity of their respective effects. MethodsWe studied 220 patients who underwent PK assessment after administration of 1 tablet of levodopa/DOPA decarboxylase inhibitor (DCI) combination, which contained 10 mg carbidopa/100 mg levodopa or 25 mg benserazide/100 mg levodopa. PK was evaluated using non-compartmental analysis. ResultsIn total, 220 PD patients (including 112 men) were studied. The mean age (±standard deviation) and mean disease duration was 68.1 ± 8.9 and 7.7 ± 5.8 years, respectively. The Cmax of levodopa was 9.0 ± 4.0 ng/mL, Tmax was 41.4 ± 40.2 min, and area under the blood concentration–time curve up to 4 h (AUC4hr) was 12.3 ± 3.7 ng/mL*4hr. Factors affecting AUC4hr were analyzed using multiple linear regression models. Age (1.1 ± 0.23 per +10 years, p = 3.1E-8), sex (2.2 ± 0.5 for female, p = 1.9E-5), DCI (1.4 ± 0.4 for benserazide, p = 0.0028), and body weight (−0.77 ± 0.22 per +10 kg, p = 5.4E-4) were significantly related to AUC4hr, while disease duration, dyskinesia status, and eGFR were not related to AUC4hr and Cmax. ConclusionFemale, aging, difference formulations of DCI, or lower body weight independently contributes to increased AUC4hr of levodopa in Japanese patients with PD in this study.