Influence of domperidone on pharmacokinetics, safety and tolerability of the dopamine agonist rotigotine

Braun, Marina; Cawello, Willi; Boekens, Hilmar; Horstmann, Rolf D.

doi:10.1111/j.1365-2125.2008.03334.x

Cited by 36 publications

(15 citation statements)

References 21 publications

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“…No formal sample size calculation was performed for this exploratory study. However, the results of previous investigations indicated that a sample size of 36 complete cases was sufficient to provide valid parameter estimations for the given population. All subjects who received ≥1 dose of study medication were included in the safety analysis.…”

Section: Methodsmentioning

confidence: 98%

No influence of the CYP2C19‐selective inhibitor omeprazole on the pharmacokinetics of the dopamine receptor agonist rotigotine

Elshoff

Cawello

Andreas

et al. 2014

Clinical Pharm in Drug Dev

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Rotigotine, a non-ergolinic dopamine receptor agonist administered transdermally via a patch, is metabolized by several cytochrome P-450 (CYP450) isoenzymes, including CYP2C19. This open-label, multiple-dose study evaluated the effect of omeprazole, a competitive inhibitor of CYP2C19, on the pharmacokinetics of rotigotine and its metabolites under steady-state conditions in healthy male subjects (of the extensive metabolizer phenotype, CYP2C19). Subjects received rotigotine 2 mg/24 hours on days 1-3, 4 mg/24 hours on days 4-12, and omeprazole 40 mg once daily on days 7-12 immediately after patch application. Blood and urine samples were collected on days 6 and 12 to evaluate rotigotine pharmacokinetic parameters alone and in the presence of omeprazole. Data from 37 subjects were available for pharmacokinetic analysis. Point estimates (90% confidence intervals, CI) for the ratios of AUC(0-24)SS and Cmax,SS of unconjugated rotigotine for the comparison rotigotine + omeprazole:rotigotine alone were close to 1 (0.9853 [0.9024, 1.0757] for AUC(0-24)SS and 1.0613 [0.9723, 1.1585] for Cmax,SS ) with 90% CIs within the acceptance range for bioequivalence (0.80, 1.25). Selective inhibition of CYP2C19 by omeprazole did not alter the steady-state pharmacokinetic profile of rotigotine or its metabolites. Thus, rotigotine dose adjustment is not required in patients receiving omeprazole, or other CYP2C19 inhibitors.

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Section: Methodsmentioning

confidence: 98%

No influence of the CYP2C19‐selective inhibitor omeprazole on the pharmacokinetics of the dopamine receptor agonist rotigotine

Elshoff

Cawello

Andreas

et al. 2014

Clinical Pharm in Drug Dev

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“…A second pathway is the formation of N‐desalkyl metabolites with subsequent conjugation [4]. There is no pharmacokinetic interaction with levodopa/carbidopa [5] and rotigotine can be co‐administered with the anti‐emetic domperidone without changes in the pharmacokinetics of rotigotine [6]. Randomized, placebo‐controlled studies have demonstrated efficacy in early Parkinson's disease (PD) as monotherapy [7, 8] and in combination with levodopa in advanced patients [9, 10].…”

Section: Introductionmentioning

confidence: 99%

Single dose pharmacokinetics of the transdermal rotigotine patch in patients with impaired renal function

Cawello¹,

Ahrweiler²,

Sułowicz³

et al. 2011

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The transdermal dopamine agonist rotigotine has been shown to be an efficacious and well tolerated treatment for Parkinson's disease and restless legs syndrome in clinical trials.• The prevalence of Parkinson's disease and restless legs syndrome increases with age.• Renal function deteriorates with age and can influence drug treatment.• Many patients with end-stage renal disease experience restless legs syndrome. WHAT THIS STUDY ADDS• The pharmacokinetic profiles of the active substance, unconjugated rotigotine, were similar in healthy subjects and subjects with renal impairment.• The results suggest that no dose adjustments are required for transdermal rotigotine in subjects with different stages of chronic renal insufficiency including patients on haemodialysis. AIMTo evaluate the influence of different stages of chronic renal insufficiency on the pharmacokinetics and safety/tolerability of the transdermally applied dopamine agonist rotigotine in an open label group comparison including 32 subjects (healthy, mild, moderate or severe impairment of renal function and patients with end-stage renal insufficiency requiring haemodialysis). METHODSAll subjects received a single transdermal 10 cm 2 patch (24 h patch-on period) containing 4.5 mg rotigotine (nominal drug release 2 mg 24 h -1 ). Main evaluations included relative bioavailability and renal elimination of rotigotine and its metabolites. RESULTSPoint estimates for the ratios between the groups with moderate to severe renal impairment and healthy subjects for the pharmacokinetic parameters AUC(0,tlast) and Cmax for the active substance unconjugated rotigotine were near 1:0.88 for AUC and 0.93 for Cmax for moderate renal impairment, 1.14 and 1.18 for severe renal impairment and 1.05 and 1.25 for end-stage renal insufficiency requiring haemodialysis. There was no correlation of these parameters with creatinine clearance. The amount of unconjugated rotigotine excreted into urine and renal clearance decreased with increasing severity of renal insufficiency but had no observable effect on total clearance as the amounts excreted were below 1% of the administered dose. Occurrence of adverse events did not increase with the degree of renal insufficiency. CONCLUSIONSThe pharmacokinetic profiles of unconjugated rotigotine were similar in healthy subjects and subjects with impaired renal function indicating that no dose adjustments are required for transdermal rotigotine in patients with different stages of chronic renal insufficiency including patients on haemodialysis.

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“…No effects on the pharmacokinetics of rotigotine were observed when it was coadministered with levodopa and carbidopa [5,21], domperidone [5,22], or omeprazole [5]. No effects on levodopa, carbidopa [5,21] or ethinylestradiol/levonorgestrel [5] pharmacokinetics were observed when they were coadministered with rotigotine.…”

Section: Pharmacokinetic Properties Of Rotigotine Transdermal Patchmentioning

confidence: 94%

Rotigotine Transdermal Patch: A Review in Restless Legs Syndrome

Garnock-Jones

2016

Drugs

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Rotigotine transdermal patch (Leganto(®), Neupro(®)) is indicated for the treatment of restless legs syndrome (RLS); this article reviews the pharmacological properties of rotigotine transdermal patch and its clinical efficacy and tolerability in patients with RLS. The transdermal patch allows for a continuous, stable release of rotigotine (avoiding first-pass metabolism), which in turn leads to continuous receptor stimulation, believed to closely mimic physiological striatal dopamine receptor function. In short-term and 6-month studies, especially at the higher dosages of 2 and 3 mg/24 h, rotigotine transdermal patch was generally associated with a significantly greater improvement in IRLS total score and CGI-S total score than placebo, and rotigotine recipients were generally more likely to respond to treatment and enter remission. In noncomparative extension studies, efficacy was sustained for ≤5 years. Rotigotine transdermal patch is generally well tolerated, and appears to have a tolerability profile that is similar to that of other non-ergolinic dopamine-receptor agonists. The most common adverse events in clinical trials included application-site reactions, nausea, headache and asthenic conditions. The drug has a relatively low risk of clinically significant augmentation of restless legs syndrome symptoms. In conclusion, rotigotine transdermal patch offers continuous administration of the drug in a daily treatment, and is a useful treatment option in patients with RLS.

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Influence of domperidone on pharmacokinetics, safety and tolerability of the dopamine agonist rotigotine

Cited by 36 publications

References 21 publications

No influence of the CYP2C19‐selective inhibitor omeprazole on the pharmacokinetics of the dopamine receptor agonist rotigotine

No influence of the CYP2C19‐selective inhibitor omeprazole on the pharmacokinetics of the dopamine receptor agonist rotigotine

Single dose pharmacokinetics of the transdermal rotigotine patch in patients with impaired renal function

Rotigotine Transdermal Patch: A Review in Restless Legs Syndrome

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