Pharmacokinetics levodopa

Cedarbaum JM, Silvestri M, Clark M, Harts A, Kutt H. L-Deprenyl, levodopa pharmacokinetics, and response fluctuations in Parkinson s disease. Clin Neuropharmacol (1990) 13, 29-35. 

Pharmacokinetics The half-life of levodopa may be prolonged following the extended-release form because of continuous absorption. In elderly subjects, the mean time to peak levodopa concentration was 2 hours for extended-release vs 0.5 hours for conventional. The maximum concentration following the extended-release form was about 35% of the conventional form. 

Pharmacology Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT), which alters the plasma pharmacokinetics of levodopa. When entacapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor (such as carbidopa), plasma levels of levodopa are greater and more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. 

Pharmacokinetics Carbidopa is rapidly and completely absorbed from the GI tract. Widely distributed. Excreted primarily in urine. Levodopa is converted to dopamine. Excreted primarily in urine. Half-life 1-2 hr (carbidopa) 1-3 hr (levodopa). 

Data from Nutt JG, Fellman JH Pharmacokinetics of levodopa. Clin Neuropharmacol 1984 7 35.)... 

Stocchi F, Barbato L, Nordera G, et al. Entacapone improves the pharmacokinetic and therapeutic response of controlled release levodopa/carbidopa in Parkinson s patients. J Neural Transm. 2004 111 173-180. 

Fate of orally administered levodopa and the effect of carbidopa, estimated from animal data. The width of each pathway indicates the absolute amount of the drug present at each site, while the percentages shown denote the relative proportion of the administered dose. The benefits of coadministration of carbidopa include reduction of the amount of levodopa diverted to peripheral tissues and an increase in the fraction of the dose that reaches the brain. (GI, gastrointestinal.) (Data from Nutt JG, Fellman JH Pharmacokinetics of levodopa. Clin Neuropharmacol 1984 7 35.)... 

J. G., Kieburtz, K., Shoulson, I. Disease progression and pharmacodynamics in Parkinson disease - evidence for functional protection with levodopa and other treatments. J Pharmacokinet Pharmacodyn 2006, 33 281 311. 

Klausner, E.A. Lavy, E. Stepensky, D. Friedman, M. Hoffman, A. Novel gastroretentive dosage forms evaluation of gastroretentivity and its effect on Levodopa absorption in humans. Pharm. Res. 2003,20 (9), 1466-1473. Klausner, E.A. Lavy, E. Stepensky, D. Cserepes, E. Barta, M. Friedman, M. Hoffman, A. Furosemide pharmacokinetics and pharmacodynamics following gastroretentive dosage form administration to healthy volunteers. J. Clin. Pharmacol 2003, 43, 711-720. 

Ruottinen HM, Rinne UK. Effect of one month s treatment with peripherally acting catechol-O-methyltransferase inhibitor, entacapone, on pharmacokinetics and motor response to levodopa in advanced parkinsonian patients. Clin Neuropharmacol 1996 19(3) 222-33. 

Carbidopa-Levodopa (Sinemet) Route PO Pregnancy Pharmacokinetic Carbidopa ... 

LeWitt PA, Nelson MV, Berchou RC, et al. Controlled-release carbidopa/levodopa (Sinemet 50/200 CR4) Clinical and pharmacokinetic studies. Neurology 1989 39(suppl 2) 45-53. 

Rabey, J.M., Schwartz, M., Graff, E., Harsat, A. and Vered, Y. (1991) The influence of bromocriptine on the pharmacokinetics of levodopa in Parkinson s disease. Clin. Neuro-pharmacol. 14 514-522. 

Robertson DRC, Higginson I, Macklin BS, Renwick AG, Waller DG, George CF. The influence of protein containing meals on the pharmacokinetics of levodopa in healthy volunteers. BrJ Clin Pharmacol (1991) 31, 413-17. 

In one study, healthy subjects were given desipramine 25 mg three times daily for 3 days then 50 mg three times daily for 10 days. For the last 5 days they were also given levodopa/carbidopa 100/25 mg three times daily and either a placebo or tolcapone 200 mg three times daily. The addition of tolcapone to combined treatment with levodopa/carbidopa and desipramine did not lead to any changes in haemodynamics or catecholamine levels, nor to any changes in desipramine pharmacokinetics. ... 

Donepezil 5 mg daily for 15 days eaused a modest 30% increase in the AUCq oflevodopa in a placebo-controlled study in 23 patients with Parkinson s disease taking levodopa/carbidopa. There was no change in car-bidopa pharmacokinetics, and the pharmacokinetics of donepezil did not differ between the patients with Parkinson s disease and a control group of healthy subjects. There was no obvious difference in adverse effects between patients with Parkinson s disease and the control subjects, and no evidence that donepezil significantly altered motor activity in those treat-... 

Okereke CS, Kirby L, Kumar D, Cullen El, Pratt RD, Hahne WA. Concurrent adm inistration of donepezil HCl and levodopa/carbidopa in patients with Parkinson s disease assessment of pharmacokinetic changes and safety following multiple oral doses. Br J Clin Pharmacol (2004) 58 (Suppl 1) 41-9. 

A study in 20 patients with Parkinson s disease taking levodopa/carbidopa found that overall there was no difference in plasma levodopa levels after bromocriptine was also taken, although some patients had either significant elevations or significant reductions in levels. However, the only adverse clinical change found was an increase in dyskinesias in the patients with elevated levodopa levels. An earlier study found no pharmacokinetic interaction between levodopa/carbidopa and bromocriptine, but it should be noted that this was a single-dose study and may not reflect long-term concurrent use. ... 

In patients on a stable dose of levodopa with a dopa-decarboxylase inhibitor, ropinirole had no effect on the pharmacokinetics of levodopa, except for a small clinically irrelevant 16% increase in maximum level. Similarly, levodopa had no effect on the pharmacokinetics of ropinirole in another group of patients. As the dose of ropinirole is increased, the dose of levodopa may be reduced gradually, by around 20% in total. ... 

The manufacturer of rotigotine reports that levodopa and carbidopa had no effect on the pharmacokinetics of rotigotine and similarly, rotigotine had no effect on tiie pharmacokinetics of either levodopa or carbidopa. However, as with other dopamine agonists, rotigotine may cause and/or exacerbate dyskinesia in patients taking levodopa and may potentiate the dopaminergic adverse reactions of levodopa. ... 

Bentue-Ferrer D, Allain H, Reymann JM, Sabouraud O, Van den Driessche J. Lack of pharmacokinetic influence on levodopa by bromocriptine. ClinNeurophannacol( 9SS) 11, 3-6. 

Entacapone and tolcapone increase the AUC of levodopa given with benserazide or carbidopa. This may require a reduction in the levodopa dose to avoid symptoms of dopamine excess when first starting the COMT inhibitor. Tolcapone increases the levels of benserazide, but neither entacapone nor tolcapone alters carbidopa pharmacokinetics. 

The effects of COMT inhibitors on the pharmacokinetics of dopa-decar-boxylase inhibitors has also been studied. Neither entacapone nor tolcapone altered the pharmacokinetics of carbidopa. However, tolcapone increased the serum levels of benserazide in patients with Parkinson s disease. The benserazide levels remained within the usual range in patients taking levodopa products containing benserazide 25 mg and tolcapone 200 mg three times daily. However, with a 50-mg dose of benserazide the AUC of benserazide was increased 4.8-fold with standard-release preparation and 2.3-fold with a controlled-release preparation. ... 

Myllyla VV, Sotaniemi KA, Illi A, Suominen K, KeranenT. Effect of entacapone, a COMT inhilitQr, on the pharmacokinetics of levodopa and on cardiovascular responses in patients with Parkinson s disease. EurJ Clin Pharmacol (1993) 45, 419-23. 

Keranen T, GonJin A, Harjola V-P, Karlsson M, Korpela K, Pentikainen PJ, Rita H, Seppala L, Wikber T. The effect of catechol-(9-methyl transferase inhibition by entacapone on the pharmacokinetics and metabolism of levodopa in healthy volunteers. Clin Neuropharmacol (1993) 16,145-56. 

Deleu D, Sarre S, Michotte Y, Ebinger G. Simultaneous in vivo microdialysis in plasma and skeletal muscle a study of the pharmacokinetic properties of levodopa by non-compartmental analysis. J Pharm Sd 1994 83 25-8. 

Stocchi, F Quinn, NP Barbato, L Patsalos, PN O Connel, MT Ruggieri, S Marsden, CD. Comparison between a Fast and a Slow Release Preparation of Levodopa and a Combination of the Two A Clinical and Pharmacokinetic Study. Clinical Neuropharmacology, 1994 17, 38-44... 

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