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

Abstract：

INTRODUCTION:There 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. METHODS:We 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. RESULTS:In 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. CONCLUSION:Female, aging, difference formulations of DCI, or lower body weight independently contributes to increased AUC4hr of levodopa in Japanese patients with PD in this study.

journal_name

Parkinsonism Relat Disord

journal_title

Parkinsonism & related disorders

authors

Nishikawa N,Iwaki H,Shiraishi T,Mukai Y,Takahashi Y,Murata M

doi

10.1016/j.parkreldis.2020.05.020

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

16-20

eissn

1353-8020

issn

1873-5126

pii

S1353-8020(20)30129-2

journal_volume

76

pub_type

杂志文章

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