MyMedR

Displaying all 4 publications

Abstract:

Sort:

Comparative bioavailability of two risperidone orodispersible tablet products after single dose administration

Tassaneeyakul W, Kumar S, Gaysonsiri D, Kaewkamson T, Khuroo A, Tangsucharit P, et al.

Int J Clin Pharmacol Ther, 2010 Sep;48(9):614-20.
PMID: 20860915

OBJECTIVES: To compare the bioavailability of two risperidone orodispersible tablet products, Risperidone 1 mg Mouth dissolving tablet, Ranbaxy (Malaysia) Sdn. Bhd., Malaysia, as a test product and Risperdal 1 mg Quicklet, Janssen Ortho LLC, Gurabo, Puerto Rico, as a reference product, in healthy male volunteers under fasting condition.
MATERIALS AND METHODS: A randomized, 2-treatment, 2-period, 2-sequence, single dose, crossover with a washout period of 2 weeks, was conducted in 24 healthy Thai male volunteers. Blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h following drug administration. Plasma concentrations of risperidone and 9-hydroxyrisperidone were determined using a validated LC-MS-MS method. The pharmacokinetic parameters of risperidone and 9-hydroxyrisperidone were determined using a non-compartmental model.
RESULTS: The geometric means ratios (%) and 90% confidence interval (CI) of the test and reference products for the log-transformed pharmacokinetic parameters, Cmax, AUC0-t and AUC0-inf of risperidone were 104.49 % (92.79% - 117.66%), 100.96 % (92.15% - 110.61 %) and 97.99 % (90.72% - 105.85%). The 90% CI of geometric means ratios of the test and reference products for the log-transformed pharmacokinetic parameters, Cmax, AUC0-t and AUC0-inf of 9-hydroxyrisperidone were 97.00%, 96.97% and 97.49%.
CONCLUSIONS: The 90% CI for the geometric means ratios (test/reference) of the log-trasformed Cmax, AUC0-t and AUC0-inf of risperidone and its major active metabolite were within the bioequivalence acceptance criteria of 80% - 125% of the US-FDA.

Matched MeSH terms: Antipsychotic Agents/pharmacokinetics*
New Insight in Improving Therapeutic Efficacy of Antipsychotic Agents: An Overview of Improved In Vitro and In Vivo Performance, Efficacy Upgradation and Future Prospects

Ei Thu H, Hussain Z, Shuid AN

Curr Drug Targets, 2018;19(8):865-876.
PMID: 27894237 DOI: 10.2174/1389450117666161125174625

Psychotic disorders are recognized as severe mental disorders that rigorously affect patient's personality, critical thinking, and perceptional ability. High prevalence, global dissemination and limitations of conventional pharmacological approaches compel a significant burden to the patient, medical professionals and the healthcare system. To date, numerous orally administered therapies are available for the management of depressive disorders, schizophrenia, anxiety, bipolar disorders and autism spectrum problems. However, poor water solubility, erratic oral absorption, extensive first-pass metabolism, low oral bioavailability and short half-lives are the major factors which limit the pharmaceutical significance and therapeutic feasibility of these agents. In recent decades, nanotechnology-based delivery systems have gained remarkable attention of the researchers to mitigate the pharmaceutical issues related to the antipsychotic therapies and to optimize their oral drug delivery, therapeutic outcomes, and patient compliance. Therefore, the present review was aimed to summarize the available in vitro and in vivo evidences signifying the pharmaceutical importance of the advanced delivery systems in improving the aqueous solubility, transmembrane permeability, oral bioavailability and therapeutic outcome of the antipsychotic agents.

Matched MeSH terms: Antipsychotic Agents/pharmacokinetics
Schizophrenia and Nicotine Dependence: What Psychopharmacological Treatment Options are Available for the Duo Perturbationes?

Theng YM, Wahab S, Wahab NAA, Sidi H, Das S

Curr Drug Targets, 2019;20(2):173-181.
PMID: 29046149 DOI: 10.2174/1389450118666171017163741

Nicotine dependence has progressively become a foremost community health interest in both the developed and developing nations due to the economic burden and health-related problems. Smoking was significantly higher among patients with schizophrenia in comparison to the general population. Nicotine dependence is not only associated with public stress, but among patients with schizophrenia, smoking brings major challenges to the management. Nicotine may diminish the therapeutic efficacy of the bioavailability of the psychopharmacological agents in-vivo. These duo perturbations, i.e. two clinical conditions co-existed may prevent psychotic symptoms remission among patients suffering from schizophrenia who smoke at the same time. The aim of this review was to highlight the role of pharmacological treatment options and strategies for patients with nicotine dependence in schizophrenia with emphasis on the underlying neurobiological process. The role of nicotine replacement therapy, i.e. norepinephrine-dopamine reuptake inhibition (NDRI) e.g. bupropion and selective partial agonist of α4β2 and full α7-nicotinic acetylcholine receptor e.g. varenicline was deliberated. An ideal choice of drug targets for patients with schizophrenia with nicotine dependence is pivotal to foster a better therapeutic alliance.

Matched MeSH terms: Antipsychotic Agents/pharmacokinetics
Preparation, characterization, and optimization of asenapine maleate mucoadhesive nanoemulsion using Box-Behnken design: In vitro and in vivo studies for brain targeting

Kumbhar SA, Kokare CR, Shrivastava B, Gorain B, Choudhury H

Int J Pharm, 2020 Aug 30;586:119499.
PMID: 32505580 DOI: 10.1016/j.ijpharm.2020.119499

The tight junctions between capillary endothelial cells of the blood-brain barrier (BBB) restricts the entry of therapeutics into the brain. Potential of the intranasal delivery tool has been explored in administering the therapeutics directly to the brain, thus bypassing BBB. The objective of this study was to develop and optimize an intranasal mucoadhesive nanoemulsion (MNE) of asenapine maleate (ASP) in order to enhance the nasomucosal adhesion and direct brain targetability for improved efficacy and safety. Box-Behnken statistical design was used to recognize the crucial formulation variables influencing droplet size, size distribution and surface charge of ASP-NE. ASP-MNE was obtained by incorporating GRAS mucoadhesive polymer, Carbopol 971 in the optimized NE. Optimized ASP-MNE displayed spherical morphology with a droplet size of 21.2 ± 0.15 nm and 0.355 polydispersity index. Improved ex-vivo permeation was observed in ASP-NE and ASP-MNE, compared to the ASP-solution. Finally, the optimized formulation was found to be safe in ex-vivo ciliotoxicity study on sheep nasal mucosa. The single-dose pharmacokinetic study in male Wistar rats revealed a significant increase in concentration of ASP in the brain upon intranasal administration of ASP-MNE, with a maximum of 284.33 ± 5.5 ng/mL. The time required to reach maximum brain concentration (1 h) was reduced compared to intravenous administration of ASP-NE (3 h). Furthermore, it has been established during the course of present study, that the brain targeting capability of ASP via intranasal administration had enhanced drug-targeting efficiency and drug-targeting potential. In the animal behavioral studies, no extrapyramidal symptoms were observed after intranasal administration of ASP-MNE, while good locomotor activity and hind-limb retraction test established its antipsychotic activity in treated animals. Thus, it can be concluded that the developed intranasal ASP-MNE could be used as an effective and safe tool for brain targeting of ASP in the treatment of psychotic disorders.

Matched MeSH terms: Antipsychotic Agents/pharmacokinetics