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An update on pharmacological, pharmacokinetic properties and drug-drug interactions of rotigotine transdermal system in Parkinson's disease and restless legs syndrome.

Elshoff JP, Cawello W, Andreas JO, Mathy FX, Braun M - Drugs (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: UCB Pharma, Alfred-Nobel-Strasse 10, 40789, Monheim am Rhein, Germany, Jan-Peer.Elshoff@ucb.com.

ABSTRACT
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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Related in: MedlinePlus

Plasma rotigotine concentrations (arithmetic mean ± SD) in 21 black African and 24 Caucasian subjects after single-dose administration of rotigotine transdermal system 2 mg/24 h
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Related In: Results  -  Collection


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Fig5: Plasma rotigotine concentrations (arithmetic mean ± SD) in 21 black African and 24 Caucasian subjects after single-dose administration of rotigotine transdermal system 2 mg/24 h

Mentions: The pharmacokinetics of a single-dose, 24-h abdominal application of transdermal rotigotine 2 mg/24 h was assessed in a single-center, open-label study of healthy black African (n = 21) and Caucasian subjects (n = 24) (data on file, UCB Pharma). Based on visual inspection, Fig. 5 shows that there was little difference between the two ethnic groups regarding the plasma concentration profile of unconjugated rotigotine. Again, a lag phase of 2 h was observed before the detection of unconjugated rotigotine in plasma. Despite the Caucasian and black African subjects being well matched demographically and both cohorts receiving the same nominal dose, mean plasma rotigotine concentrations at most time points in the Caucasian group were slightly higher than in the black African group. Pharmacokinetic analysis of AUC ratios revealed that total systemic exposure to rotigotine in black African subjects may be slightly lower than in Caucasian subjects (Table 2).Fig. 5


An update on pharmacological, pharmacokinetic properties and drug-drug interactions of rotigotine transdermal system in Parkinson's disease and restless legs syndrome.

Elshoff JP, Cawello W, Andreas JO, Mathy FX, Braun M - Drugs (2015)

Plasma rotigotine concentrations (arithmetic mean ± SD) in 21 black African and 24 Caucasian subjects after single-dose administration of rotigotine transdermal system 2 mg/24 h
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4382528&req=5

Fig5: Plasma rotigotine concentrations (arithmetic mean ± SD) in 21 black African and 24 Caucasian subjects after single-dose administration of rotigotine transdermal system 2 mg/24 h
Mentions: The pharmacokinetics of a single-dose, 24-h abdominal application of transdermal rotigotine 2 mg/24 h was assessed in a single-center, open-label study of healthy black African (n = 21) and Caucasian subjects (n = 24) (data on file, UCB Pharma). Based on visual inspection, Fig. 5 shows that there was little difference between the two ethnic groups regarding the plasma concentration profile of unconjugated rotigotine. Again, a lag phase of 2 h was observed before the detection of unconjugated rotigotine in plasma. Despite the Caucasian and black African subjects being well matched demographically and both cohorts receiving the same nominal dose, mean plasma rotigotine concentrations at most time points in the Caucasian group were slightly higher than in the black African group. Pharmacokinetic analysis of AUC ratios revealed that total systemic exposure to rotigotine in black African subjects may be slightly lower than in Caucasian subjects (Table 2).Fig. 5

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: UCB Pharma, Alfred-Nobel-Strasse 10, 40789, Monheim am Rhein, Germany, Jan-Peer.Elshoff@ucb.com.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus