[Inter- and intraindividual pharmacokinetic variations in the treatment of Parkinson's disease].

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Nomoto M, Nakatsuka A, Nagai M, Yabe H, Moritoyo T, Moritoyo H, Nisikawa N

[Inter- and intraindividual pharmacokinetic variations in the treatment of Parkinson's disease].

Rinsho Shinkeigaku. 2005 Nov;45(11):895-8.

PubMed ID

16447756 [ View in PubMed

]

Abstract

In the treatment of Parkinson's disease, levodopa, DCI, MAO-B inhibitor, COMT inhibitors, dopamine receptor agonists, amantadine, anticholinergics have been applied and new drugs are being developed. Levodopa is still the golden standard in the treatment of Parkinson's disease. The study on levodopa bioavailability showed 3-4 times differences in individual patients. Drug-food interactions are prominent in levodopa. Low protein food increased levodopa bioavailability and improved no ON or delayed ON in the treatment of Parkinson's disease. Vitamine C or magnesium did not alter the bioavailability of levodopa. The bioavailability of levodopa between the levodopa/carbidioa (100/12.5) group and the levodopa/benserazide (100/25) group was studied in patients with Parkinson's disease by population PK study. C(max) of levodopa in levodeopa/benserazide group was twice as high as in levodopa/carbidopa group. Domperidone, a dopamine receptor antagonist applied as an antiemetic inceases vowel movement. The effect of domperidone on levodopa bioavailability was studied, and the combination of domperidone with levodopa increased AUC of levodopa. Clarythromycin or grape fruit juice inhibits both of CYP3A4 and P-glycoprotein which work on metabolism and absorption of drugs. Coadministration of clarythromycin with ergot alkaloids such as cabergoline or bromocriptine increased the AUC up to 2-3 times. Amantadine is excreted through kidney without being metabolized and renal function is the most important factor in the blood concentration of amantadine. In elder women with the body weight of 50 kg or less, creatinine clearance is less than 50 ml/min even though the serum creatinine is within the normal range. Selegiline is metabolized through CYP2D6 and 3A4. Coadministration of qunidine, cimetidine, maclorides, antifungals, grape fruit juice increase the bioavailability of selegiline and may augment the antiparkinsonian effect.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Selegiline	Cytochrome P450 2D6	Protein	Humans	Unknown	Substrate Inhibitor	Details

Food Interactions

Drug	Interaction
Cabergoline	Exercise caution with grapefruit products. Cabergoline is partially metabolized through the CYP3A4 pathway. Therefore coadministration with grapefruit, a CYP3A4 inhibitor, may increase its serum concentration.
Cabergoline	Exercise caution with St. John's Wort. Cabergoline is partially metabolized through the CYP3A4 pathway. Therefore coadministration with St. John's Wort, a CYP3A4 inducer, may reduce its serum concentration.