Gender Differences in Levodopa Pharmacokinetics in Levodopa-Naïve Patients With Parkinson’s Disease

[Esperanto]

The differences in plasma LD concentrations between men and women over time.

Original research article Front. Med., 31 May 2022

frontiersin.org/articles/10...

On my search for the Pharmacokinetics, pharmacodynamics of the various C/L medications, I came across this remarkable research from last year. Maybe someone else has already posted this, in which case I apologise. For me it was new and the results reaffirmed my suspicion that after all these years the PD medication is still often based on standard procedures and is hardly tailored to the individual according to the latest (and even older) scientific insights. Because you apparently have to do that yourself, collecting this type of information is crucial to understanding and handling your possible over- and under-dosing. 🍀

Results

The LD concentrations were measured in plasma from 35 Caucasian patients (19 men and 16 women) with PD. All of them were LD-naïve patients and received a single dose of oral LD/benserazide (100/25 mg) formulation.

The study population appeared to be homogenous for the age and duration of the disease. No differences were found in BMI median value between men and women, while women had a median value of BW lower than men. Daily energy consumption and lean mass were higher in men than in women, while women showed higher fat mass compared with men without reaching a statistical significance. There was no difference in PD symptoms, monoamine oxidase-B inhibitors (iMAO-B), dopamine agonists (DA) use, and comorbidities between genders. The main characteristics of the study population are listed in Table 1. No differences were found in dietary habits (data not shown).

Conclusion

Taken together, our findings provide novel insights into gender differences in LD pharmacokinetics, possibly contributing to the later development of motor complications and dyskinesia in PD. The results refer to parameters measured at the first drug intake of patients enrolled in an ongoing study with a 2-year follow-up. Future analyses will allow us to assess whether the highlighted differences translate into different patterns of adverse events in men and women.

[Esperanto]

Remarkably, there have been no responses to this research from you. The same (0 replies) with the post of BeedieBird “Interesting Gender Research Findings RE: Levodopa Absorption Rates” 4 months ago

healthunlocked.com/cure-par...

I myself found the results rather shocking. It means that on average women are twice as sensitive to the C/L medication and can suffice with much lower medication. Given the automatisms where the C/L is prescribed by neurologists, with little nuance for the person, you might expect more dyskinesia to be detected in women. That turns out to be the case. Dyskinesia is found to be more common in women as in men, even more than 2 times as much after the age of 70.

Gender differences in tardive dyskinesia: a critical review of the literature

academic.oup.com/schizophre...

[Stillstandingstill in reply to Esperanto]

I did see this and it's quite shocking, but I didn't feel there was anything I could add at the time. I'm afraid that women have historically been an afterthought in some areas of medicine and beyond, such as car and equipment safety design.

[Esperanto in reply to Stillstandingstill]

I was more concerned with realising that women could be at risk of overdose if doctors are unaware of this phenomenon. So actually more as a warning. I do indeed find it incomprehensible that no further research has been done to my knowledge after the aforementioned 1994 study on the cause of an increased risk of dyskinesia in women because no difference is made in C/L dosage between men and women. Or were you all aware of this?

Also in a later study from 2006 “Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study” the link with possible (unnecessary) overdose is not made: “It is unclear why women are more susceptible than men to develop PDD, as we and others have reported, but there is evidence that the female hormonal status may underlie this susceptibility, possibly by modifying the individual dyskinetic sensitivity to levodopa through estrogens.

jamanetwork.com/journals/ja...

In my next life I will study neurology!

[Esperanto]

“Risk of developing PD is twice as high in men than women, but women have a higher mortality rate and faster progression of the disease. Moreover, motor and nonmotor symptoms, response to treatments and disease risk factors differ between women and men. “ As even 25 years later it is found in: “Parkinson’s Disease in Women and Men: What’s the Difference?” With the following conclusion: “Increasing experimental and clinical evidence supports the idea that PD differs between women and men. Not only do men and women experience the disease differently, but different mechanisms seem to be involved in the pathogenesis of the disease. Nevertheless, we are still far away from the actual understanding of what underlies such differences. Studies in this area are under-represented, both from the clinical and research perspective, especially for females…..”

ncbi.nlm.nih.gov/pmc/articl... of developing PD is,differ between women and men.