Ziprasidone: efficacy, tolerability, and emerging data on wide-ranging effectiveness.

Mt. Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
Expert Opinion on Pharmacotherapy (Impact Factor: 2.86). 03/2005; 6(2):337-46. DOI: 10.1517/14656566.6.2.337
Source: PubMed

ABSTRACT Ziprasidone is the fifth atypical antipsychotic to become available in the US market. This compound is a serotonin-dopamine-receptor antagonist, with greater affinity for the 5-HT(2A) receptor than the dopamine D2 receptor. Similar to aripiprazole, this compound also has agonist activity at the serotonin 5-HT(1A) receptor. This affinity has the potential to have particularly beneficial effects on cognitive and affective abnormalities in schizophrenia. Oral and short-acting intramuscular formulations are available. This compound has recently been approved for the treatment of acute mania as well as for schizophrenia. Ziprasidone is associated with low weight gain and a low potential to change lipid and glucose levels. Long-term tolerability data have indicated that initial concerns regarding QTc (corrected cardiac output) prolongation are not a major issue. Recent data have indicated that this compound has short-term antipsychotic efficacy that is equivalent to other members of the class, also with evidence of cognitive enhancement. Finally, longer term data has indicated that ziprasidone is successful in the prevention of relapse and has sustained cognitive benefits. Several issues remain to be addressed, including the efficacy of once-daily dosing, the need to take the medication with food, and the correct dosing strategy.

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    ABSTRACT: The purpose of this work was to develop self-nanomulsifying drug delivery systems (SNEDDS) in sustained-release pellets of ziprasidone to enhance the oral bioavailability and overcome the food effect of ziprasidone. Preformulation studies including screening of excipients for solubility and pseudo-ternary phase diagrams suggested the suitability of Capmul MCM as oil phase, Labrasol as surfactant, and PEG 400 as co-surfactant for preparation of self-nanoemulsifying formulations. Preliminary composition of the SNEDDS formulations were selected from the pseudo-ternary phase diagrams. The prepared ziprasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized ziprasidone-SNEDDS were used to prepare ziprasidone-SNEDDS sustained-release pellets via extrusion-spheronization method. The pellets were characterized for SEM, particle size, droplet size distribution and zeta potential. In vitro drug release studies indicated the ziprsidone-SNEDDS sustained-release pellets showed sustained release profiles with 90% released within 10 h. The ziprsidone-SNEDDS sustained-release pellets were administered to fasted and fed beagle dogs and their pharmacokinetics were compared to commercial formulation of Zeldox as a control. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolonged actions and enhanced bioavailability with no food effect was achieved simultaneously in ziprsidone-SNEDDS sustained-release pellets compared with Zeldox in fed state. The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment.
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    ABSTRACT: Abstract Objective: The purpose of this work was to develop a controlled release of ziprasidone with no food effect by the osmotic release strategy. Methods: The solution of ziprasidone and poloxamer188 (P188) with different weight ratios was spray-dried to form solid dispersion of ziprasidone (SD-ZIP). The SD-ZIP was characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (X-RD) and solubility testing. The SD-ZIP osmotic pump tablets were prepared by wet granulation method. The effect of formulation variables on the release characteristic was investigated. The SD-ZIP osmotic pump tablets were administered to fasted and fed beagle dogs and their pharmacokinetics were compared to commercial formulation Zeldox® as a control. Results: The results of DSC and X-RD indicated that ziprasidone resides in P188 with no crystalline changes. Solubility studies demonstrated that the solubility of SD-ZIP was substantially improved compared to ziprasidone and physical mixtures of ziprasidone and P188. The optimized formulation and drug release profiles of SD-ZIP osmotic pump tablets in different medium were obtained which showed typical osmotically controlled release and could fitted to zero-order kinetics with good linear correlation. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolong actions and no food effect was achieved simultaneously in SD-ZIP osmotic pump tablet compared with Zeldox®. Conclusion: The SD-ZIP osmotic pump tablet could be able to enhance the bioavailability in the fasted state and showed sustained release with prolonged actions.
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    ABSTRACT: Since schizophrenia is considered one of the top ten causes of disease-related disability in the world, the development of second-generation (atypical) antipsychotics (SGAs) has increased the hopes of psychiatrists. SGAs, however, cannot be considered a unique pharmacological class since each SGA has many complex pharmacologic actions, only some of which are shared with other SGAs. Even though manyantipsychotics have similar efficacy on average, prescribers may be able to achieve better than average results by considering differences in selecting a specific drug for a specific patient. Clinicians know that each patient is unique. In order to achieve best outcomes for the individual patient, the better therapy is the therapy tailored for the single patient. With this article, we provide information on a relatively new antipsychotic ziprasidone released in 2001 by Pfizer for the treatment of schizophrenia. Compared with other first line atypical antipsychotics ziprasidone has a unique profile due to potent interaction with serotonergic receptors and lesser action upon α1 adrenergic, H1 and M1 antagonist activities. This paper describes the development of ziprasidone, its unique properties and its metabolically-friendly profile including its receptor binding affinities, pharmacokinetics, CNS activity results of clinical efficacy and relevant clinical trials. Safety, efficacy and patient preference are also examined. The available literature on ziprasidone of the last five years is reviewed.
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