Evidence map›Paper›PMID 33093598›Full record

Trial reportScientific reports2020

Population pharmacokinetics of levodopa gel infusion in Parkinson's disease: effects of entacapone infusion and genetic polymorphism.

M Senek, D Nyholm, E I Nielsen

Open access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Observational
  8. Article
  9. Article
  10. Monotherapy with infusion therapies - useful or not?Journal of neural transmission (Vienna, Austria : 1996) · 2024
    Review
  11. Article
  12. Article
  13. Current and novel infusion therapies for patients with Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2023
    Review
  14. Review
  15. Parkinson's disease therapy: what lies ahead?Journal of neural transmission (Vienna, Austria : 1996) · 2023
    Review
  16. Clinical Pharmacology of Entacapone (Comtan) From the FDA Reviewer.The international journal of neuropsychopharmacology · 2022
    Article
  17. Review
  18. Review
  19. An updated calculator for determining levodopa-equivalent dose.Neurological research and practice · 2021
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

M SenekDepartment of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
D NyholmDepartment of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden. dag.nyholm@neuro.uu.se.ORCID 0000-0001-9776-7715
E I NielsenDepartment of Pharmacy, Uppsala University, Uppsala, Sweden.
Uppsala University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Levodopa-entacapone-carbidopa intestinal gel (LECIG) provides continuous drug delivery through intrajejunal infusion. The aim of this study was to characterize the population pharmacokinetics of levodopa following LECIG and levodopa-carbidopa intestinal gel (LCIG) infusion to investigate suitable translation of dose from LCIG to LECIG treatment, and the impact of common variations in the dopa-decarboxylase (DDC) and catechol-O-methyltransferase (COMT) genes on levodopa pharmacokinetics. A non-linear mixed-effects model of levodopa pharmacokinetics was developed using plasma concentration data from a double-blind, cross-over study of LCIG compared with LECIG in patients with advanced Parkinson's disease (n = 11). All patients were genotyped for rs4680 (polymorphism of the COMT gene), rs921451 and rs3837091 (polymorphisms of the DDC gene). The final model was a one compartment model with a high fixed absorption rate constant, and a first order elimination, with estimated apparent clearances (CL/F), of 27.9 L/h/70 kg for LCIG versus 17.5 L/h/70 kg for LECIG, and apparent volume of distribution of 74.4 L/70 kg. Our results thus suggest that the continuous maintenance dose of LECIG, on a population level, should be decreased by approximately 35%, to achieve similar drug exposure as with LCIG. An effect from entacapone was identified on all individuals, regardless of COMT rs4680 genotype. The individuals with higher DDC and COMT enzyme activity showed tendencies towards higher levodopa CL/F. The simultaneous administration of entacapone to LCIG administration results in a 36.5% lower apparent levodopa clearance, and there is a need for lower continuous maintenance doses, regardless of patients' COMT genotype.

Indexed as

CatecholsDrug Delivery SystemsNitrilesPolymorphism, GeneticCarbidopaCatechol O-MethyltransferaseCross-Over StudiesDopa DecarboxylaseDouble-Blind MethodDrug CombinationsFemaleGelsGenotypeHumansLevodopaMaleCarbidopacarbidopa, levodopa drug combinationCatechol O-MethyltransferaseCatecholsCOMT protein, humanDopa DecarboxylaseDrug CombinationsentacaponeGelsLevodopaNitriles

Identifiers

PMID33093598
PMCPMC7582154
OpenAlexW3094171252

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.