Abstract:
PURPOSE:The preclinical pharmacokinetic and pharmacodynamic properties of a potent fluoroketolide RBx14255 against Streptococcus pneumoniae and Haemophilus influenzae was compared with telithromycin and human clinical dose was predicted for preclinical development. METHODS:The in vitro pharmacokinetic characterization was performed for solubility, Caco-2 permeability, microsomal stability, CYP inhibition and plasma protein binding. In vivo pharmacokinetic studies were performed in Swiss albino mice, Sprague Dawley rats and Beagle dogs. The pharmacodynamic studies were carried out in mouse against S. pneumoniae in systemic infection and against S. pneumoniae and H. influenzae in rat lung infection models. RESULTS:RBx14255 showed superior potency and efficacy in mouse and rat infection models. RBx14255 showed pH dependent solubility (0.41 mg/mL at pH 6.8 and >1 mg/mL at pH 1.2), moderate Caco-2 permeability (A to B: 12 nm/s) with high efflux ratio. It showed high plasma protein binding (>97%) in mouse and low binding (45- 70%) in rat, dog and human. The compound is mainly metabolized through CYP3A4. Pharmacokinetic parameters and absolute bioavailability of both, RBx14255 and telithromycin are similar in mouse. Both the ketolides showed low plasma clearance (18% of the normal hepatic blood flow rate) in mouse, moderate to high clearance in rat and dog. Mean oral bioavailability was high in mouse (≥85%), moderate in rat (RBx14255: 15% and telithromycin: 51%) and high to moderate in dog (RBx14255: 98% and telithromycin: 56%). The predicted efficacious dose for a 70 kg man ranges from 124 mg BID to 226 mg BID. CONCLUSION:RBx14255 displayed significantly better pharmacodynamics which correlates with the pharmacokinetic properties against S. pneumoniae and H. influenzae as compared to telithromycin. The predicted human efficacious doses are in the range of 124-226 mg, making it amenable to oral dosage form drug in human. This could be a promising clinical candidate for future studies.
journal_name
J Pharm Pharm Sciauthors
Chaira T,Barman T,Samuel Raj Vdoi
10.18433/jpps30942subject
Has Abstractpub_date
2020-01-01 00:00:00pages
206-219issn
1482-1826journal_volume
23pub_type
杂志文章abstract:PURPOSE:To examine the inhibitory effects of star fruit (Averrhoa carambola) juice towards seven major cytochrome P450 (CYP) isoforms and NADPH-cytochrome P450 reductase (CPR). METHODS:The inhibitory effects of star fruit juice (0.5 to 5%, v/v) against the activities of seven CYP isoforms including CYP1A2, CYP2A6, CYP...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j30593
更新日期:2007-01-01 00:00:00
abstract::Chitosan has prompted the continuous movement for the development of safe and effective drug delivery systems because of its unique physicochemical and biological characteristics. The primary hydroxyl and amine groups located on the backbone of chitosan allow for chemical modification to control its physical propertie...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章,评审
doi:10.18433/j3jc7c
更新日期:2010-01-01 00:00:00
abstract:PURPOSE:DEET and oxybenzone are two essential active ingredients in repellent and sunscreen products. The percutaneous permeation of the two compounds across human skin from five commercially available repellent and sunscreen products was investigated in vitro. METHODS:Diffusion studies were carried out at 37 degrees ...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract:PURPOSE:Because oxytocin (OT) is potentially useful in cardiovascular therapy but has hormonal roles on the cardiovascular and renal systems, we characterized its pharmacokinetic (PK) properties as a function of dose. METHODS:A single intravenous bolus of OT was given at doses of 200, 300, 500, 1000, 3000, 5000 and 10...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3pk5x
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:Inhalation anesthetics have been shown to have electrical suppressant effects on excitable membranes such as the cardiac conduction system. Therefore, the anesthetized patient or laboratory animal may respond differently to cardiac drugs when compared with their conscious counterparts. The purpose of this ...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract::Purpose - The CEIBA cocktail consisting of caffeine (CAF), omeprazole (OZ), dextromethorphan (DM) and losartan (LOS) was previously proposed for the clinical phenotyping of five major human cytochrome P450 (CYP) isoenzymes. This work aimed to assess the usefulness of CEIBA cocktail to study non-clinical drug interacti...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/J3D313
更新日期:2016-01-01 00:00:00
abstract:PURPOSE:The aim of the study was the prediction of human intestinal permeability and fraction absorbed of oral dose using single-pass intestinal perfusion technique (SPIP) in rats. METHODS:Permeability coefficients in anaesthetized rats were determined for 14 compounds. Drug solution in phosphate buffered saline (PBS)...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract::Cannabis has been used for its medicinal purposes since ancient times. Its consumption leads to the activation of Cannabis receptors CB1 and CB2 that, through specific mechanisms can lead to modulation and progression of inflammation or repair. The novel findings are linked to the medical use of Cannabis in gastrointe...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/jpps31242
更新日期:2020-01-01 00:00:00
abstract:PURPOSE:A randomized cross-over, double blind placebo controlled study of smoked cannabis was carried out on occasional cannabis smokers. The objective of this research was to describe the pharmacokinetic parameters of THC and its metabolites in plasma, oral fluid and urine, from samples obtained simultaneously to prov...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章,随机对照试验
doi:10.18433/J3F31D
更新日期:2016-01-01 00:00:00
abstract:PURPOSE:Comparison of the effects of one year treatment with sibutramine compared to placebo on insulin resistance parameters, body weight, glycemic control, and lipid profile, in type 2 diabetic patients. METHODS:Two hundred and forty-six patients with uncontrolled type 2 diabetes mellitus in therapy with different o...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.18433/j3388p
更新日期:2010-01-01 00:00:00
abstract:PURPOSE:To determine the merits of a robot at the community pharmacy in a quasi-experiment. METHOD:The applied methods for data-collection were barcode-time measurements, direct observations, time-interval studies, and tally at a Dutch community pharmacy. The topics consisted of workload, waiting times, congestion, sl...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2006-01-01 00:00:00
abstract:PURPOSE:The adrenoceptor family, as one of the main contributors in regulating the noradrenergic system, has been studied in involvement of depression and its treatment. A functional polymorphism of G1165C on beta adrenoceptor (βAR) enhances post receptor signalling and is assumed to be involved in pharmacotherapy of d...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/J3W31F
更新日期:2017-01-01 00:00:00
abstract:PURPOSE:Aim of this study is to investigate the mechanism of self-emulsification through rheological analysis of intermediate liquid crystalline (LC) phase formed during self-emulsification process. METHODS:Binary system of tween 80 (T80) and imwitor 742 (I742) was used and different SES were prepared with I742 at 10,...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j30w2p
更新日期:2009-01-01 00:00:00
abstract:PURPOSE:Clinical studies have suggested that proton pump inhibitors may decrease levothyroxine absorption and an in vitro study suggested that the effect of pH on dissolution may differ with formulation. To determine the impact of formulation on the pharmacokinetics of levothyroxine in altered gastric pH conditions, th...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j36p5m
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:To perform a review describing the pharmacokinetic (PK) parameters and covariates of interest of the eight first choice β-lactams (BL) antibiotics for treatment of severe infections in pediatric population. Pediatric sepsis and septic shock reportedly affect 30% of children admitted to pediatric intensive ca...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/jpps30927
更新日期:2020-01-01 00:00:00
abstract::Hypochlorhydria is a condition where the production of hydrochloric acid in the stomach is decreased. As a result, the intragastric pH is elevated. This condition can be due to a series of causes, such as disease (gastric mucosal infection caused by Helicobacter pylori and is prominent in AIDS patients), ethnicity, ag...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/jpps30227
更新日期:2018-01-01 00:00:00
abstract:PURPOSE:The aim of this study was to determine the cause of the decline in phenolsulfonphthalein (PSP) excretion in Long-Evans Cinnamon (LEC) rats. METHODS:The uptake of PSP into rat renal basolateral membrane vesicles (BLMV) was studied. Cyclosporin A (CYA) was used to modulate an ATP-dependent primary active transpo...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2004-07-13 00:00:00
abstract:PURPOSE:To evaluate the inhibitory activity of active compounds isolated from Cinnamomum cassia bark against lens aldose reductase and compare to that of three commercially available compounds (cinnamyl alcohol, trans -cinnamic acid, and eugenol) and quercitrin as aldose reductase inhibitors. The IC (50) value of cinna...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract:PURPOSE:To assess the predicted rate and the factors associated with bleeding events among patients with non-valvular atrial fibrillation (NVAF) receiving dabigatran therapy. METHODS:This retrospective cohort study includes adult patients of two tertiary hospitals in Malaysia. Potential study subjects were identified ...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/J3TP9Q
更新日期:2017-01-01 00:00:00
abstract::PURPOSE. Animal-derived drugs are the major source of biological products and traditional medicine, but they are often difficult to identify, causing confusion in the clinical application. Among these medicinal animals, a number of animal species are endangered, leading to the destruction of biodiversity. The identifi...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3n017
更新日期:2011-01-01 00:00:00
abstract::Life-threatening fungal infections have increased dramatically in recent decades in immunocompromised patients. An estimated 40% of all deaths from hospital-acquired infections are due to infections caused by opportunistic fungi. The current treatment options are either causing serious toxicity, or becoming inactive a...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3h010
更新日期:2008-07-06 00:00:00
abstract::In noncompartmental analysis, poor characterization of the terminal elimination rate constant (Kel) will lead to biased results for half-life and total exposure (AUCinf), providing incorrect relative bioavailability and bioequivalence conclusions. We set out to determine if the sampling scheme duration was crucial for...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3fg63
更新日期:2011-01-01 00:00:00
abstract::The microneedles technology has found applications in many health-related fields. For example, their application in drugs and vaccines delivery as well, as the determination of biomarkers, has been reported. They also have a place in the dermatology and cosmetic areas such as the treatment of wounds from burns, scars,...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章,评审
doi:10.18433/jpps29610
更新日期:2018-01-01 00:00:00
abstract:PURPOSE:Drug release from nanosystems at the sites of either absorption or effect biophase is a major determinant of its biological action. Thus, in vitro drug release is of paramount importance in gaining insight for the systems performance in vivo. METHODS:A novel in vitro in vivo correlation, IVIVC, model denoted a...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3np5n
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:Tramadol Hydrochloride is a widely-used centrally acting analgesic drug, which has some features of being a P-gp substrate. The present study evaluates the functional involvement of P-gp in CNS distribution of tramadol. METHODS:The possible involvement of P-glycoprotein in brain distribution of tramadol was ev...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3d60r
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:A series of delta-valerolactones has been synthesized in good yields, by reaction of ethyl acetoacetate with several aldehydes in presence of LDA. METHODS AND RESULTS:The in vivo analgesic activity of these compounds has been evaluated. The results indicate that the lactones synthesized showed an important ant...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2005-04-08 00:00:00
abstract:PURPOSE:Status epilepticus (SE) is characterized by recurrent seizure activity and can be drug- resistant. Knowledge of neuronal and metabolic activity of the brain during SE may be helpful to improve medical care. We here report the effects of three anti-seizure drugs on changes of acetylcholine energy metabolites and...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/jpps30439
更新日期:2019-01-01 00:00:00
abstract:PURPOSE:To systematically review and quantitatively synthesize associations between HLA genotypes and oxcarbazepine-induced cutaneous adverse drug reactions (OXC-cADRs), including Stevens-Johnson syndrome (SJS) and maculopapular rash. METHODS:Studies investigating associations between HLA genotypes and OXC-cADRs were ...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章,meta分析
doi:10.18433/J36S7D
更新日期:2018-01-01 00:00:00
abstract:PURPOSE:Vigabatrin, an anti-epileptic drug with poor UV absorptivity, is used as a model drug to investigate parameters affecting quantitative determination of cationic drugs using capillary zone electrophoresis with indirect UV detection. METHODS:All experiments were performed on a HP 3D CE instrument equipped with a...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2005-08-03 00:00:00
abstract:PURPOSE:Oseltamivir is a prodrug that requires metabolic activation but there is little information on whether natural health products interact to prevent the biotransformation by the carboxylesterase. METHODS:HPLC-DAD-ESI-MSD and fluorometric assays were used to determine if 50-pooled mixed gender human liver microso...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3zp42
更新日期:2010-01-01 00:00:00