Gender Differences in Levodopa Pharmacokinetics in Levodopa-Naïve Patients With Parkinson's Disease.
Front Med (Lausanne)
; 9: 909936, 2022.
Article
in En
| MEDLINE
| ID: mdl-35712091
ABSTRACT
Background:
Levodopa (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 andMethods:
This is a multicentric study enrolling patients with PD, who were LD-naïve 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.Results:
Thirty-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 (ß = 1.559116, 95% CI 0.8314479 2.286785; p < 0.0001) and body mass index (BMI) (ß = -0.0970631, 95% CI -0.1733004 -0.0208258; p = 0.014) significantly predicted AUC. Only female sex significantly predicted Cmax (ß = 1,582.499, 95% CI 731.581 2,433.417; p = 0.001). Moreover, only BMI significantly predicted t 1/2 (ß = 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 (ß = 0.1300486, 95% CI 0.0172322 0.242865; p = 0.027), but not in men.Conclusion:
This study provides novel insights on gender differences in LD pharmacokinetics, possibly contributing to the later development of motor complications and dyskinesia in PD.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Aspects:
Determinantes_sociais_saude
/
Ethics
Language:
En
Journal:
Front Med (Lausanne)
Year:
2022
Document type:
Article
Affiliation country: