[Inter- and intraindividual pharmacokinetic variations in the treatment of Parkinson's disease].
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.
Nomoto
Masahiro
M
University Department of Clinical Pharmacology and Neurology.
Nakatsuka
Akiko
A
Nagai
Masahiro
M
Yabe
Hayato
H
Moritoyo
Takashi
T
Moritoyo
Hiroyoko
H
Nisikawa
Noriko
N
D000978:Antiparkinson Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004294:Domperidone / Q000493:pharmacokinetics; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D004347:Drug Interactions; D006801:Humans; D007206:Individuality; D007980:Levodopa / Q000493:pharmacokinetics*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism
D000978:Antiparkinson Agents; D018492:Dopamine Antagonists; D007980:Levodopa; D004294:Domperidone