Targeting STEAP1 Protein in Human Cancer: Current Trends and Future Challenges.

Cancer is a global health issue that impairs the life quality of patients and origins thousands of deaths annually worldwide. Six-transmembrane epithelial antigen of the prostate (STEAP1) was identified to be overexpressed in several types of cancers, namely in prostate cancer (PCa). Considering its secondary structure, associated with its location in the cell membrane, has been suggested a role in intercellular communication between tumour cells. Taking into account its high specificity and overexpression in human cancers, STEAP1 is nowadays a promising candidate to be imposed as a therapeutic target. Several strategies have been developed during the last few years for targeting STEAP1, including antibody-drug conjugates, monoclonal antibodies (mAbs), DNA vaccines and small noncoding RNAs (ncRNAs). This review presents the current knowledge about STEAP1 protein expression in human tissues, its biochemical properties and targeting strategies with the purpose to evaluate its potential as therapeutic agent for cancer.

Dissolution of omeprazole from delayed-release solid oral dosage forms.

The evaluation of the biopharmaceutical quality of omeprazole enteric-coated products (granules in capsules) with respect to its dissolution characteristics is not specifically regulated in any of the most common official pharmacopoeia. USP 23 includes a general monograph for enteric-coated products. This paper reports the evaluation of the medium pH effect on the dissolution rates of omeprazole from four omeprazole-containing products of different manufacturers. It is concluded that the USP 23 recommended dissolution procedure for enteric-coated products is not suitable due to the degradation of omeprazole under such conditions. Furthermore, the medium with pH 8.0 showed different dissolution rates not observed at pH 7.4, allowing discrimination between products of different manufacturers.

Bioequivalence evaluation of two omeprazole enteric-coated formulations in humans.

Omeprazole, a proton pump inhibitor, effectively suppresses the gastric acid secretion in the parietal cells of the stomach. Several previously published papers focus on the pharmacokinetics of the drug and its interactions with physiological aspects or with other drugs. The increasing number of omeprazole containing products available in the market, raises questions of therapeutic equivalence and/or generic substitution. The bioequivalence evaluation between two or more formulations provides information about in vivo performance. In a favorable decision regarding bioequivalence, the products are considered to have a similar therapeutic efficacy when used under the same therapeutic conditions. This paper reports the design, results and some important aspects involved in a bioequivalence study between two solid oral formulations from different manufacturers. Some important findings were the high intra-subject variability observed for Cmax and the variability observed between subject profiles, probably caused by the multi-unit type of formulations studied.

Determination of apovincaminic acid in human plasma by high-performance liquid chromatography.

An isocratic high-performance liquid chromatographic method is described for the quantitative analysis of low concentrations of apovincaminic acid (AVA) in blood plasma. AVA, interfering plasma components and primidone (used as the internal standard) were separated on a reversed-phase column of LiChrospher 60 RP-Select B (125 mm x 3 mm i.d.; 5 microns) (Merck). A UV-Vis detector was used at a wavelength of 254 nm. Each chromatographic separation was completed in 14 min and the results showed a relative recovery which varied between 95.9 and 116%, a good overall precision (relative standard deviation, 7.00%) and sensitivity over a linear range of 5.00-300 ng ml-1 (R = 0.999) for AVA in plasma. The method was applied to the analysis of plasma samples obtained from healthy subjects treated with one single oral dose of 20 mg of vinpocetine. The results indicate the method to be suitable for pharmacokinetic studies.

A comparative bioavailability study to estimate the influence of an antacid on droxicam pharmacokinetics.

The influence of an antacid on droxicam pharmacokinetics was investigated in 12 healthy male volunteers. A two way cross-over study was performed after the oral administration of 20 mg of droxicam (Ombolan capsules) and droxicam together with an antacid (Mucal powder). The plasma concentrations of piroxicam, the active moiety of droxicam, were determined by a high-performance liquid chromatographic method. The pharmacokinetic parameter values (mean +/- RSD) of piroxicam after administration of droxicam alone were: AUC0-->infinity = 125.5 +/- 25.1 micrograms.h/l, Cmax = 2.08 +/- 19.9 micrograms/l, tmax = 7.08 +/- 36.8 h and t1/2 = 46.3 +/- 27.0 h. Following administration of droxicam together with the antacid the values obtained for the same parameters were: AUC0-->infinity = 135.1 +/- 24.1 micrograms.h/l. Cmax = 1.85 +/- 23.9 micrograms/l, tmax = 8.17 +/- 34.9 h and t1/2 = 52.0 +/- 22.4 h. These results indicate that concurrent administration of the antacid does not significantly change the bioavailability and pharmacokinetics of droxicam.