Influence of Meal Ingestion Time on Pharmacokinetics of Orally Administered Levodopa in Parkinsonian Patients

Baruzzi, Agostino; Contin, Manuela; Riva, R.; Procaccianti, Gaetano; Albani, Fiorenzo; Tonello, C.; Zoni, Elisabetta; Martinelli, Paolo

doi:10.1097/00002826-198712000-00004

Cited by 81 publications

(54 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Because L-dopa is an amino acid derivative, the possibility that protein-rich meal ingestion alters oral L-dopa absorption and brain bioavailability has been documented. 23,24 DHA is an essential polyunsaturated fatty acid that is rapidly taken up by the body and rapidly incorporated into triglycerides in the blood circulation. Although the active transport of DHA into the brain is not well understood, strong evidence indicate that DHA easily enters into the brain.…”

Section: Discussionmentioning

confidence: 99%

Docosahexaenoic acid reduces levodopa‐induced dyskinesias in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine monkeys

Samadi

Grégoire

Rouillard

et al. 2006

Annals of Neurology

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Docosahexaenoic acid reduces levodopa‐induced dyskinesias in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine monkeys

Samadi

Grégoire

Rouillard

et al. 2006

Annals of Neurology

View full text Add to dashboard Cite

show abstract

“…In fasting PD patients with motor complications the levodopa absorption from the gut is rapid with time to peak plasma levodopa concentrations (T max ) within 60 min (36,(38)(39)(40). The T max increases threefold and the maximal concentration (C max ) is decreased 30 % when levodopa is administrated after meal compared to fasting (38).…”

Section: Levodopa In the Peripherymentioning

confidence: 99%

“…The T max increases threefold and the maximal concentration (C max ) is decreased 30 % when levodopa is administrated after meal compared to fasting (38). Very low levels of orally administrated levodopa are excreted in faeces indicating a high absorption of levodopa (41,42).…”

Section: Levodopa In the Peripherymentioning

confidence: 99%

“…Only app. 1 % of levodopa, given as monotherapy, is eliminated in the urine unmetabolized, indicating a high peripheral metabolism (38,42,43). Levodopa is nearly undetectable in plasma 5 h after dosing.…”

Section: Levodopa In the Peripherymentioning

confidence: 99%

“…Without an enzyme inhibitor only app. 1 % of the amount of levodopa, given orally is available to cross the BBB (38,42,43). The COMTinhibitor entacapone has been shown to increase [18F]-6-L-fluorodopa in striatum in PD patients with premedication with the DDI carbidopa (66).…”

Section: Levodopa In the Brainmentioning

confidence: 99%

See 2 more Smart Citations

Levodopa pharmacokinetics -from stomach to brain : A study on patients with Parkinson’s disease

Nord¹

2017

Linköping University Medical Dissertations

View full text Add to dashboard Cite

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and it is caused by a loss of dopamine (DA) producing neurons in the basal ganglia in the brain. The PD patient suffers from motor symptoms such as tremor, bradykinesia and rigidity and treatment with levodopa (LD), the precursor of DA, has positive effects on these symptoms. Several factors affect the availability of orally given LD. Gastric emptying (GE) is one factor and it has been shown to be delayed in PD patients resulting in impaired levodopa uptake. Different enzymes metabolize LD on its way from the gut to the brain resulting in less LD available in the brain and more side effects from the metabolites. By adding dopa decarboxylase inhibitors (carbidopa or benserazide) or COMT-inhibitors (e.g. entacapone) the bioavailability of LD increases significantly and more LD can pass the blood-brain-barrier and be converted to DA in the brain. It has been considered of importance to avoid high levodopa peaks in the brain because this seems to induce changes in postsynaptic dopaminergic neurons causing disabling motor complications in PD patients. More continuously given LD, e.g. duodenal or intravenous (IV) infusions, has been shown to improve these motor complications. Deep brain stimulation of the subthalamic nucleus (STN DBS) has also been proven to improve motor complications and to make it possible to reduce the LD dosage in PD patients. In this doctoral thesis the main purpose is to study the pharmacokinetics of LD in patients with PD and motor complications; in blood and subcutaneous tissue and study the effect of GE and PD stage on LD uptake and the effect of continuously given LD (CDS) on LD uptake and GE; in blood and cerebrospinal fluid (CSF) when adding the peripheral enzyme inhibitors entacapone and carbidopa to LD infusion IV; in brain during STN DBSand during oral or IV LD treatment. To conclude, LD uptake is more favorable in PD patients with less severe disease and GE is delayed in PD patients. No obvious relation between LD uptake and GE or between GE and PD stage is seen and CDS decreases the LD levels. Entacapone increases the maximal concentration of LD in blood and CSF. This is more evident with additional carbidopa and important to consider in avoiding high LD peaks in brain during PD treatment. LD in brain increases during both oral and IV LD treatment and the DA levels follows LD well indicating that PD patients still have capacity to metabolize LD to DA despite probable pronounced nigral degeneration. STN DBS seems to increase putaminal DA levels and together with IV LD treatment also increases LD in brain possibly explaining why it is possible to decrease LD medication after STN DBS surgery.Parkinsons sjukdom (PS) är en av de vanligaste s.k. neurodegenerativasjukdomarna och orsakas av förlust av dopamin(DA)producerande nervceller i hjärnan. Detta orsakar motoriska symptom såsom skakningar, stelhet och förlångsammade rörelser. Levodopa (LD) är ett ämne, som kan omvandlas till DA i hjärnan och ge symptomlindrin...

show abstract

Standard and Controlled-Release Levodopa/Carbidopa in Patients With Fluctuating Parkinson's Disease on a Protein Redistribution Diet

1991

View full text Add to dashboard Cite

Influence of Meal Ingestion Time on Pharmacokinetics of Orally Administered Levodopa in Parkinsonian Patients

Cited by 81 publications

References 0 publications

Docosahexaenoic acid reduces levodopa‐induced dyskinesias in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine monkeys

Docosahexaenoic acid reduces levodopa‐induced dyskinesias in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine monkeys

Levodopa pharmacokinetics -from stomach to brain : A study on patients with Parkinson’s disease

Standard and Controlled-Release Levodopa/Carbidopa in Patients With Fluctuating Parkinson's Disease on a Protein Redistribution Diet

Contact Info

Product

Resources

About