Abstract: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 h… Show more
“…Serum plasma concentrations of unconjugated and total rotigotine were stable over the maintenance phase, which indicates lack of accumulation, and were similar to those seen in patients with RLS with and without impaired renal function. 16,34 This supports earlier demonstrations that rotigotine dose adjustments are not required for patients with reduced kidney function, including those receiving hemodialysis. 34 Elimination of rotigotine from plasma is comparable in healthy individuals and patients with different stages of chronic kidney diseases, and rotigotine is not removed by the dialysis procedure.…”
Section: Discussionsupporting
confidence: 82%
“…The observed w16point reduction in IRLS score with rotigotine corresponded to a shift from severe (IRLS, 21-30) to mild symptoms (IRLS, 1-10). 22 In comparison, patients receiving placebo had an w9-point reduction in IRLS score, with a shift from severe to moderate (IRLS, [11][12][13][14][15][16][17][18][19][20] symptoms. These results were consistent with those for the CGI-1, with the majority of rotigotine-treated patients (and 50% of patients receiving placebo) improving to a category of mildly, borderline, or not at all ill.…”
Section: Discussionmentioning
confidence: 99%
“…[13][14][15] Rotigotine is a nonergot dopamine receptor agonist administered by a transdermal patch, which provides continuous drug delivery with stable plasma levels over 24 hours. 16 The efficacy of rotigotine transdermal patch in moderate to severe primary RLS has been demonstrated in two 6-month double-blind studies that assessed symptom severity by subjective rating scales 17, 18 and in a 4-week double-blind polysomnography study that used the PLM Index (PLMI; PLM per hour in bed) as the primary outcome measure. 19 The current study was a randomized controlled trial to investigate the efficacy of rotigotine on PLM, sleep, RLS symptoms, and quality of life in patients with RLS and ESRD requiring hemodialysis.…”
Rotigotine improved periodic limb movements and RLS symptoms in the short term among ESRD patients requiring hemodialysis in a small-scale study. No dose adjustments are necessary for hemodialysis patients.
“…Serum plasma concentrations of unconjugated and total rotigotine were stable over the maintenance phase, which indicates lack of accumulation, and were similar to those seen in patients with RLS with and without impaired renal function. 16,34 This supports earlier demonstrations that rotigotine dose adjustments are not required for patients with reduced kidney function, including those receiving hemodialysis. 34 Elimination of rotigotine from plasma is comparable in healthy individuals and patients with different stages of chronic kidney diseases, and rotigotine is not removed by the dialysis procedure.…”
Section: Discussionsupporting
confidence: 82%
“…The observed w16point reduction in IRLS score with rotigotine corresponded to a shift from severe (IRLS, 21-30) to mild symptoms (IRLS, 1-10). 22 In comparison, patients receiving placebo had an w9-point reduction in IRLS score, with a shift from severe to moderate (IRLS, [11][12][13][14][15][16][17][18][19][20] symptoms. These results were consistent with those for the CGI-1, with the majority of rotigotine-treated patients (and 50% of patients receiving placebo) improving to a category of mildly, borderline, or not at all ill.…”
Section: Discussionmentioning
confidence: 99%
“…[13][14][15] Rotigotine is a nonergot dopamine receptor agonist administered by a transdermal patch, which provides continuous drug delivery with stable plasma levels over 24 hours. 16 The efficacy of rotigotine transdermal patch in moderate to severe primary RLS has been demonstrated in two 6-month double-blind studies that assessed symptom severity by subjective rating scales 17, 18 and in a 4-week double-blind polysomnography study that used the PLM Index (PLMI; PLM per hour in bed) as the primary outcome measure. 19 The current study was a randomized controlled trial to investigate the efficacy of rotigotine on PLM, sleep, RLS symptoms, and quality of life in patients with RLS and ESRD requiring hemodialysis.…”
Rotigotine improved periodic limb movements and RLS symptoms in the short term among ESRD patients requiring hemodialysis in a small-scale study. No dose adjustments are necessary for hemodialysis patients.
“…Four studies have evaluated the drug–drug interaction potential between rotigotine and levodopa/carbidopa, domperidone, oral contraceptives, cimetidine, and omeprazole under steady-state conditions [ 44 – 47 ]. According to the generally accepted regulatory requirements, bioequivalence was concluded (i.e., no relevant interaction) if the 90 % CIs for the ratio of the geometric means for unconjugated rotigotine alone versus in combination with test drugs, or vice versa, were within the 80–125 % acceptance range for all primary pharmacokinetic parameters [ 48 ].…”
Section: Drug–drug Interactionsmentioning
confidence: 99%
“… Fig. 6 Mean (±SD) steady-state rotigotine plasma concentrations with and without co-administration of a levodopa/carbidopa (100/25 mg) [ 44 ], b domperidone (10 mg/day) [ 45 ], c cimetidine (400 mg bid), and d omeprazole (40 mg/day) [ 47 ]. bid twice daily …”
This narrative review reports on the pharmacological and pharmacokinetic properties of rotigotine, a non-ergolinic D3/D2/D1 dopamine receptor agonist approved for the treatment of early- and advanced-stage Parkinson’s disease (PD) and moderate to severe restless legs syndrome (RLS). Rotigotine is formulated as a transdermal patch providing continuous drug delivery over 24 h, with a plasma concentration profile similar to that of administration via continuous intravenous infusion. Absolute bioavailability after 24 h transdermal delivery is 37 % of the applied rotigotine dose. Following a single administration of rotigotine transdermal system (24-h patch-on period), most of the absorbed drug is eliminated in urine and feces as sulphated and glucuronidated conjugates within 24 h of patch removal. The drug shows a high apparent volume of distribution (>2500 L) and a total body clearance of 300–600 L/h. Rotigotine transdermal system provides dose-proportional pharmacokinetics up to supratherapeutic dose rates of 24 mg/24 h, with steady-state plasma drug concentrations attained within 1–2 days of daily dosing. The pharmacokinetics of rotigotine transdermal patch are similar in healthy subjects, patients with early- or advanced-stage PD, and patients with RLS when comparing dose-normalized area under the plasma concentration–time curve (AUC) and maximum plasma drug concentration (Cmax), as well as half-life and other pharmacokinetic parameters. Also, it is not influenced in a relevant manner by age, sex, ethnicity, advanced renal insufficiency, or moderate hepatic impairment. No clinically relevant drug–drug interactions were observed following co-administration of rotigotine with levodopa/carbidopa, domperidone, or the CYP450 inhibitors cimetidine or omeprazole. Also, pharmacodynamics and pharmacokinetics of an oral hormonal contraceptive were not influenced by rotigotine co-administration. Rotigotine was generally well tolerated, with an adverse event profile consistent with dopaminergic stimulation and use of a transdermal patch. These observations, combined with the long-term efficacy demonstrated in clinical studies, support the use of rotigotine as a continuous non-ergot D3/D2/D1 dopamine receptor agonist in the treatment of PD and RLS.
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