Yet Another Doctor Blog On The Internet

Pharmacological prevention of atherothrombotic events in patients with peripheral arterial disease.

2017-05-19

The following pharmacokinetic parameters refer to the geometric mean values for both formulations. Mean Cmax value of 10 mg OD alfuzosin was 15.8 ng/ml at a median t(max) of 9.0 h; Cmax was higher and reached earlier from 2.5 mg alfuzosin TID: 19.3 ng/ml, 19.7 ng/ml and 20.3 at 1.0 hour after each dosing, respectively. Mean AUC(0-24) values after OD and TID were 228.3 and 226.0 ng x h/ml, respectively. Based on AUC(0-24) values corrected by the administered daily dose, the relative bioavailability of alfuzosin OD was 75.7% with a 90% confidence interval of 68.0 - 84.3%. Non-corrected AUC(0-24) values were bioequivalent with a ratio estimate of 101.0% and a 90% confidence interval of 90.7 - 112.5%. The higher daily dose compensated for the loss of bioavailability observed with the OD formulation. Mean t1/2z value was longer for the OD (8.9 h) than the TID formulation (6.9 h). Variability between individuals was similar for the 2 formulations. Both dose regimens were well tolerated.

Prospective case-control study.

In BPH there is a growth of both glandular and stromal components. Most of adrenoceptors sites are in the fibromuscular stroma. So the higher is the stromal/epithelial ratio, the more effective will alpha-blockers be. There in an indirect way of stimating this ratio without performing a biopsy. Bearing in mind that PSA is produced by the prostatic epithelium, the lower PSA density (PSAd), the higher the stromal/epithelial ratio and the higher alpha-blocker activity. We pretend to study if PSAd is useful for predicting the response to alpha-blockers in BPH.

The purpose of this study was to evaluate the incidence, risk factors, and impact of intraoperative floppy iris syndrome (IFIS) on surgical performance.

The relative cytotoxic potency order was prazosin = doxazosin > terazosin = silodosin = alfuzosin > tamsulosin on both cell types, but LNCaP cells were significantly more sensitive to these effects than PC-3 cells. Prazosin and doxazosin increased levels of apoptotsis and autophagy in both cell lines, and activated EphA2 receptors in PC-3 cells. Autophagy contributed to survival of LNCaP, but promoted cell death in PC-3 cells. Treatment with prazosin (30 μM) altered the expression of several cell stress-related proteins: elevating phospho-p38α and reducing S6 kinase in both cell lines. Surprisingly some proteins were differentially affected in the two prostate cancer cell lines: Akt and p27 increasing and HIF-1α decreasing in LNCap cells but not PC-3, while ADAMTS1 was increased in PC-3 cells only.

Up-to-date analysis of clinical placebo-controlled or direct comparative studies with alpha1-adrenoceptor antagonists in patients with LUTS suggestive of BPO derived from a MEDLINE search in October 1998. All retrieved studies were analyzed with regard to efficacy and tolerability. Efficacy was evaluated by the percentage improvement in total symptom score and Qmax (mean end of study value relative to mean baseline value). Tolerability was evaluated by means of study withdrawal rate because of adverse events and the incidence of vasodilatatory adverse events (e.g. dizziness and orthostatic hypotension).

Prazosin and doxazosin demonstrated cytotoxic actions on both castration-resistant PC-3 and androgen-sensitive LNCap prostate cancer cells. The mechanisms involved included changes in a number of proliferation and apoptosis regulatory proteins. The role of autophagy depended on the cell type, but contributed to cell death in PC3 cells.

We have recapitulated drug-induced cardiotoxicity profiles for healthy subjects, long QT syndrome, hypertrophic cardiomyopathy, and dilated cardiomyopathy patients at the single cell level for the first time. Our data indicate that healthy and diseased individuals exhibit different susceptibilities to cardiotoxic drugs and that use of disease-specific hiPSC-CMs may predict adverse drug responses more accurately than the standard human ether-a-go-go-related gene test or healthy control hiPSC-CM/hESC-CM screening assays.

This large study conducted during general practice on Spanish BPH patients confirms the efficacy on LUTS and good safety profile of SR alfuzosin, especially its low incidence of postural symptoms and no deleterious effect on sexual function.

The nanoparticles displayed high production yields (86.99-94.63% w/w) with a reasonable drug incorporation efficiency ranged from 92.86 to 97.75%. The nanoparticles were readily reconstituted in aqueous solution with a particle size range of 122.1-260.0 nm and a zeta potential range of -21.6 to -36.6 mV indicating a good colloidal stability. No drug crystals were detectable in the scanning electron micrographs revealing successful encapsulation of alfuzosin into casein nanoparticles which was confirmed by differential scanning calorimetry. The nanoparticles succeeded in prolonging the drug release that could be controlled by modulating the genipin crosslinking degree. The release data showed a good fit into Higuchi release kinetics with non-Fickian type of drug diffusion.