No abstract

؊1 . The presence of P-gp considerably impacted the active renal secretion of LEV but had only a minor impact on the efflux from the lung following intratracheal dosing. Our results strongly support the idea of a role of efflux transporters other than P-gp contributing to LEV's tissue penetration into the prostrate.

No abstract

Summary. An accurate and reliable LC-MS/MS assay was firstly developed and validated for quantitative determination of a new antimalarial prototype drug, 3β-hydroxyurs-12-en-28-oic acid (LAFIS 01), in rat plasma. Dexamethasone was employed as internal standard. Simple protein precipitation by acetonitrile for the sample preparation was used. Effective separation was achieved with Phenomenex Luna C 18 (50 × 2 mm, 5 μm) column. The mobile phase consisted of (A) water and (B) acetonitrile, both containing 0.1% acetic acid, delivered by gradient elution. The column temperature was maintained at 40 °C. The LAFIS 01 was monitored by electrospray ionization interface, operating in the negative mode (ESI−) in multiple reactions monitoring (MRM), checking the transitions 455 > 455 for LAFIS 01 and 451 > 361 for the IS. Once LAFIS 01 demonstrated low fragmentation by collision-induced dissociation (CID) nonpresenting abundant highintensity fragments to meet the desired concentration levels quantification, only pseudomolecular ion was monitored. The flow rate was 500 μL min −1 . The lower limit of quantitation achieved was 10 ng mL −1 and linearity was observed from 10 to 500 ng mL −1 . The relative standard deviation (RSD) values of the intra-and inter-assay precisions of the method were below 8.42 and 7.94%, respectively. The accuracy ranged from 92.05 to 102.94%. The extraction recovery of LAFIS 01 and IS was up to 90%. The method showed linearity, precision, accuracy, sensitivity, and stability required to quantify LA-FIS 01 in preclinical pharmacokinetic study.

No abstract

A specific, precise, and accurate LC-UV method was developed and validated to assay raloxifene hydrochloride in rat plasma. Raloxifene was analyzed after liquid-liquid extraction and quantified by reversed phase liquid chromatography (C18 column) using acetonitrile and ammonium acetate buffer 0.05 M (pH 4.0) as mobile phase at a flow rate of 1 mL.min-1 and UV detection at 287 nm. Retention times of raloxifene and internal standard (dexamethasone) were approximately 11 min and 14 min, respectively. Linearity was checked for a concentration range between 25 ng.mL-1 and 1000 ng.mL-1. Intra-and inter-day precision had relative standard deviation lower than 10% and 15%, respectively. Recovery from plasma was higher than 90%. Accuracy values were 98.21%, 99.70%, and 102.70% for lower, medium, and upper limits of quantification, respectively. Limit of quantification was 25 ng.mL-1. Drug stability was analyzed at room temperature using plasma kept in a freezer at-80 °C for 45 days after processing for 6 h and three freeze-thaw cycles. The advantages of the method developed include stability under different conditions and low limit of quantification. Its applicability was confirmed by the analysis of raloxifene levels in plasma samples in a designed pharmacokinetic study in rats after intravenous administration (5 mg.kg-1).

Antimicrobial prophylactic dosing of morbidly obese patients may differ from normal weighted individuals owing to alterations in drug tissue distribution. Drug subcutaneous tissue distribution can be investigated by microdialysis patients and animals. The need for cefazolin prophylactic dose adjustment in obese patients remains under discussion. The paper describes the validation of an HPLC-UV method for cefazolin quantification in plasma and microdialysate samples from clinical and pre-clinical studies. A C column with an isocratic mobile phase was used for drug separation, with detection at 272 nm. Total and unbound cefazolin lower limit of quantitation was 5 μg/mL in human plasma, 2 μg/mL in rat plasma, and 0.5 and 0.025 μg/mL in human and rat microdialysate samples, respectively. The maximum intra- and inter-day imprecisions were 10.7 and 8.1%, respectively. The inaccuracy was <9.7%. The limit of quantitation imprecision and inaccuracy were < 15%. Cefazolin stability in the experimental conditions was confirmed. Cefazolin plasma concentrations and subcutaneous tissue penetration were determined by microdialysis in morbidly obese patients (2 g i.v. bolus) and diet-induced obese rats (30 mg/kg i.v. bolus) using the method. This method has the main advantages of easy plasma clean-up and practicability and has proven to be useful in cefazolin clinical and pre-clinical pharmacokinetic investigations.

Uma das estratégias utilizadas para melhoria da segurança do paciente, principalmente na identificação e prevenção de eventos adversos relacionados a medicamentos, é a conciliação medicamentosa. A identificação de discrepâncias entre os medicamentos em uso pelo paciente antes da admissão hospitalar e os medicamentos prescritos durante a internação evitam danos que podem ser permanentes e promovem a segurança do paciente. O objetivo do estudo foi identificar, utilizando da conciliação medicamentosa, possíveis discrepâncias e interações medicamentosas em pacientes internados em unidade clínica de um hospital público do Sul do Brasil, por meio de um estudo transversal, de caráter descritivo e prospectivo, no qual os pacientes foram entrevistados sobre os medicamentos em uso antes da internação e comparando com o que foi prescrito. A maioria dos pacientes era homens, idosos e com doenças cardiovasculares como doença de base. Dos 50 entrevistados, 94% apresentaram ao menos uma discrepância. Dos 153 medicamentos discrepantes, 66,7% foram classificados como discrepâncias intencionais e 33,3% como discrepâncias não intencionais. Os medicamentos que atuam no sistema cardiovascular foram os mais frequentes, nas discrepâncias e nas possíveis interações medicamentosas. Os pacientes polimedicados foram os que apresentaram número maior de possíveis interações medicamentosas. A identificação dessas discrepâncias demonstrou a importância da realização da conciliação medicamentosa e da intervenção do farmacêutico na prevenção de eventos adversos relacionados a medicamentos.