Pharmacokinetics and tolerability of intramuscular, oral and intravenous aripiprazole in healthy subjects and in patients with schizophrenia.

BACKGROUND AND OBJECTIVE: Patients with schizophrenia or bipolar disorder who are experiencing acute behavioural emergencies often require intramuscular injection of antipsychotics for rapid symptom resolution. The efficacy and tolerability of intramuscular aripiprazole injection has been established in agitated inpatients with schizophrenia or bipolar I disorder. The main objective of the two clinical pharmacology studies reported here was to evaluate the pharmacokinetics of aripiprazole after intramuscular dosing in healthy subjects and in patients with schizophrenia, and after intravenous and oral dosing in healthy subjects. SUBJECTS AND METHODS: Study 1 was an open-label, randomized, three-treatment crossover study in healthy subjects (n = 18) to assess the bioavailability and pharmacokinetics of intramuscular aripiprazole 5 mg and oral aripiprazole 5 mg relative to intravenous aripiprazole 2 mg. Study 2 was an open-label, nonrandomized, escalating-dose study in patients with schizophrenia (n = 32) to evaluate the pharmacokinetics of intramuscular aripiprazole across a range of doses (from 1 mg to 45 mg). MAIN OUTCOME MEASURES: The noncompartmental pharmacokinetic parameters for plasma concentrations of aripiprazole and its active metabolite dehydro-aripiprazole were determined. Safety and tolerability data are also summarized. RESULTS: In study 1, the geometric mean values for the absolute bioavailability of aripiprazole following oral and intramuscular administration were 0.85 and 0.98, respectively. Intramuscular aripiprazole demonstrated more rapid attainment of plasma aripiprazole concentrations than oral aripiprazole (78% and 5% of peak plasma concentration [C(max)] values at 0.5 hours postdose, respectively). The area under the plasma concentration-time curve (AUC) in the first 2 hours was 90% higher after intramuscular administration than after oral administration. For dehydro-aripiprazole, the AUC over the collection interval values were higher, the times to reach the C(max) values were later and the C(max) values were similar for the intramuscular and oral formulations. In study 2, the proportionality of the C(max) and AUC to doses ranging from 1 mg to 45 mg suggests a linear pharmacokinetic profile for intramuscular aripiprazole. CONCLUSION: More rapid absorption was observed following intramuscular aripiprazole injection than following oral dosing. These results support the recently reported efficacy of intramuscular aripiprazole for managing agitation in patients with schizophrenia or bipolar I disorder.

A review of the literature on the selegiline transdermal system: an effective and well-tolerated monoamine oxidase inhibitor for the treatment of depression.

OBJECTIVE: To provide a narrative review of the properties of the selegiline transdermal system (STS) for the treatment of depression and its subtypes. BACKGROUND: Monoamine oxidase inhibitors (MAOIs) once represented the mainstay of therapy for the treatment of major depressive disorder (MDD). However, despite their efficacy, these agents fell from favor due to the risk of acute hypertensive reactions following ingestion of foods containing high concentrations of tyramine. Recent efforts to develop MAOIs that overcome these limitations have resulted in the introduction of the first transdermal formulation of the MAOI selegiline for the treatment of MDD. DATA SOURCES: A PubMed literature search was conducted in January 2007 using the keyword selegiline transdermal system. STUDY SELECTION: Articles retrieved were reviewed and selected for inclusion based on their being randomized, double-blind, placebo-controlled studies that appeared between the years 2000 and 2007 and examined efficacy, safety, and tolerability data from clinical trials of patients with MDD who were treated with the STS. Four articles, including 3 acute trials and 1 long-term prevention of relapse trial, were included in this review based on these criteria. CONCLUSIONS: The selegiline transdermal system provides several advantages compared to orally administered MAOIs, including minimal interaction with dietary tyramine and prolonged exposure to the parent compound, while offering a favorable side effect profile. As a result, treatment at the lowest effective dose of 6 mg/24 hours can be administered without the need for dietary modifications.

The selegiline transdermal system (emsam): a therapeutic option for the treatment of major depressive disorder.

Although monoamine oxidase inhibitors (MAOIs) at one time represented the mainstay of therapy for major depressive disorder (MDD), the risk of acute hypertensive reactions following the ingestion of tyramine-rich foods and the consequent need to restrict dietary tyramine represent a barrier to their use. In this article, we present an overview of the efficacy and safety of a transdermal formulation of the MAOI selegiline for the treatment of MDD. Transdermal delivery of selegiline at the effective dose of 6 mg every 24 hours eliminates the need for a tyramine-restricted diet. Our emphasis on potential drug-drug interactions and contraindications should be useful to prescribers who counsel patients with MDD.