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

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 (AUC) was 12.3 ± 3.7 ng/mL*4hr. Factors affecting AUC 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 AUC, while disease duration, dyskinesia status, and eGFR were not related to AUC and Cmax.

CONCLUSION

Female, aging, difference formulations of DCI, or lower body weight independently contributes to increased AUC of levodopa in Japanese patients with PD in this study.