Gender Differences in Levodopa Pharmacokinetics in Levodopa-Naive Patients With Parkinson's Disease

被引：22

作者：

Conti, Valeria ^{[1
]}

Izzo, Viviana ^{[1
]}

Russillo, Maria Claudia ^{[2
]}

Picillo, Marina ^{[2
]}

Amboni, Marianna ^{[2
]}

Scaglione, Cesa L. M. ^{[3
]}

Nicoletti, Alessandra ^{[4
]}

Cani, Ilaria ^{[3
]}

Cicero, Calogero E. ^{[4
]}

De Bellis, Emanuela ^{[1
]}

Charlier, Bruno ^{[1
]}

Giudice, Valentina ^{[1
]}

Somma, Gerardina ^{[2
]}

Corbi, Graziamaria ^{[5
]}

Barone, Paolo ^{[2
]}

Filippelli, Amelia ^{[1
]}

Pellecchia, Maria Teresa ^{[2
]}

机构：

[1] Univ Salerno, Surg & Dent Scuola Med Salernitana, Dept Med, Clin Pharmacol Unit, Baronissi, Italy

[2] Univ Salerno, Surg & Dent Scuola Med Salernitana, Dept Med, Neurosci Sect, Baronissi, Italy

[3] Bellaria Hosp, IRCCS Ist Sci Neurolog Bologna, UOC Neurol Clin, Bologna, Italy

[4] Univ Catania, Dept Med, Neurol Unit, AOU Policlin San Marco, Catania, Italy

[5] Univ Molise, Dept Med & Hlth Sci, Campobasso, Italy

来源：

FRONTIERS IN MEDICINE | 2022年 / 9卷

关键词：

gender; Parkinson's disease; levodopa; pharmacokinetics; motor; non-motor fluctuations; dyskinesia; body weight; body mass index; BODY-WEIGHT; DYSKINESIA;

D O I：

10.3389/fmed.2022.909936

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundLevodopa (LD) is the most effective drug in the treatment of Parkinson's disease (PD). Unfortunately, prolonged use of LD leads to complications, mainly motor/non-motor fluctuations (MNMF) and dyskinesias (DYS). Women seem more prone to develop such LD-related complications. Nonetheless, there is a paucity of prospective studies examining gender-related predictors of MNMF and DYS. Among several factors, which concur with a very complex scenario, changes in LD pharmacokinetics influence the drug's effectiveness. The present study aimed to assess gender-related differences in LD pharmacokinetics in patients with PD at their first-ever intake of LD. Materials and MethodsThis is a multicentric study enrolling patients with PD, who were LD-naive and received a single dose of LD/benserazide (100/25 mg) formulation. All participants gave their written informed consent, and the study was approved by the local Ethics Committees. To measure plasma LD concentrations and pharmacokinetic parameters (AUC, Cmax, Tmax, t(1/2)), fasting blood samples were collected before drug intake and then at 8-time points until 260 min. LD concentrations were measured by ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). Multiple linear regression analyses were performed to identify the predictors of the parameters. ResultsThirty-five patients (16 women and 19 men) were consecutively enrolled. Area under curve (AUC) and maximum plasma concentration (Cmax) were significantly higher in women than men (p = 0.0006 and p = 0.0014, respectively). No statistically significant difference was found regarding Tmax and t(1/2). Multiple linear regression analyses revealed that female sex (beta = 1.559116, 95% CI 0.8314479 2.286785; p < 0.0001) and body mass index (BMI) (beta = -0.0970631, 95% CI -0.1733004 -0.0208258; p = 0.014) significantly predicted AUC. Only female sex significantly predicted Cmax (beta = 1,582.499, 95% CI 731.581 2,433.417; p = 0.001). Moreover, only BMI significantly predicted t(1/2) (beta = 0.0756267, 95% CI 0.0143407 0.1369126; p = 0.017). Stratifying by gender, BMI was confirmed to significantly predict t(1/2) in women (beta = 0.1300486, 95% CI 0.0172322 0.242865; p = 0.027), but not in men. ConclusionThis study provides novel insights on gender differences in LD pharmacokinetics, possibly contributing to the later development of motor complications and dyskinesia in PD.

引用

页数：10

共 21 条

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