The evaluation of apomorphine for the treatment of erectile dysfunction.

INTRODUCTION: Erectile dysfunction (ED) is a common condition affecting men. Apomorphine is one of the oral medications that has been used in the management of ED, though over recent years, its use in the management of ED has dwindled. AREAS COVERED: The authors review the evidence available for the use of apomorphine in the management of ED. A Medline search was performed searching for the articles related to the use of apomorphine in the treatment of ED from 2000 to present. The article reviews the erectogenic properties of apomorphine and evaluates its efficacy, suitability and tolerability in management of patients with ED. EXPERT OPINION: Apomorphine SL is more effective than placebos in treating ED and is generally well tolerated in the sublingual formulation, causing tolerable side effects. Newer nasal-spray formulations provide faster efficacy. Its efficacy in patients with multiple co-morbidities is more limited. However, it is not as effective as PDE5-I in the treatment of ED. Its most significant strength is its safety profile. It may have a niche in the treatment ED in patients who have failed treatment with, or are intolerant to other well-established pharmacological treatment for ED (e.g., PDE5-Is). Apomorphine is not a first-line treatment option for patients with ED, especially as it is no more widely available in the western world.

Combined strategies of apomorphine diester prodrugs and nanostructured lipid carriers for efficient brain targeting.

Our aim is to develop nanostructured lipid carriers (NLCs) for loading the apomorphine diester prodrugs, diacetyl apomorphine (DAA) and diisobutyryl apomorphine (DIA), into the brain. NLCs were prepared using sesame oil/cetyl palmitate as the lipid matrices. Experiments were performed with the objective of evaluating the physicochemical characteristics, drug release, safety and brain-targeting efficacy of the NLCs. The size of regular NLCs (N-NLCs) was 214 nm. The addition of Forestall (FE) and polyethylene glycol (PEG) to the NLCs (P-NLCs) increased the particle diameter to 250 nm. The zeta potentials of N-NLCs and P-NLCs were respectively shown to be - 21 and 48 mV. Diester prodrugs were more lipophilic and more chemically stable than the parent apomorphine. The hydrolysis study indicated that the prodrugs underwent bioconversion in plasma and brain extract, with DAA exhibiting faster degradation than DIA. Sustained release was achieved through the synergistic effect of integrating strategies of prodrugs and NLCs, with the longer carbon chain showing the slower release (DIA < DAA). None of the NLCs tested here exhibited a toxicity problem according to the examination of neutrophil lactate dehydrogenase (LDH) release and hemolysis. Results of a bioimaging study in mice showed that P-NLCs largely accumulated in the brain. The distribution duration of the fluorescent dye in the brain region was also prolonged by the nanocarriers.

Pharmacokinetics and clinical efficacy of rectal apomorphine in patients with Parkinson's disease: a study of five different suppositories.

The pharmacokinetics and clinical effects of apomorphine after rectal administration were determined in five patients with idiopathic Parkinson's disease (PD). Three different pharmaceutical formulations were tested: a rectal solution of apomorphine (10 or 15 mg), a gelatin suppository (25 and 50 mg), and a Witepsol-H15 suppository (50 and 100 mg). The pharmacokinetics of apomorphine were determined by measuring plasma concentrations using a sensitive and specific high-performance liquid chromatography method. The mean bioavailability varied between 14.7% and 40.2%, which was the bioavailability until the end of clinical benefit. Also, despite the differences in dose, the values of the Cmax were similar, with average values of 12.7-25.6 ng/ml. Wide differences in Tmax were observed, with values varying between 16 min for the enema and 127.5 min for the Witepsol-H15 100-mg suppository. The time course of the clinical effect was determined by assessing the time needed for walking a 25-m course and by calculating a tremor and dyskinesia score. Onset of effect was similar for each of the preparations, with an average onset time of 14-28 min. Significant differences with respect to the duration of the effect were observed. The duration of effect after administration of the Witepsol-H15 100-mg suppository was 156 +/- 43 min versus 50 +/- 13 min after rectal administration of the apomorphine solution. These results show that rectal administration of apomorphine may present an alternative to subcutaneous administration. The sustained-release properties of the Witepsol-H15 suppositories are especially of interest in the treatment of on-off fluctuations in PD.