Combination of Olanzapine Pamoate with Melatonin and Metformin: Quantitative Changes in Rat Adipose Tissue.

Olanzapine is one of the atypical antipsychotics widely used in the treatment of schizophrenia and has been associated with metabolic changes as adverse effects, including hyperglycemia, dyslipidemia, and weight gain. In a batch of adult female Wistar rats, we studied the prolonged-release intramuscular olanzapine pamoate induced quantitative changes of visceral and subcutaneous adipose tissue. We also assessed the effects of the combinations of olanzapine pamoate with melatonin, metformin, and melatonin plus metformin, administered by gastric gavage. A higher mean weight of the visceral and subcutaneous adipose tissue per animal was noted in the olanzapine pamoate exposed group compared to controls. The association with melatonin, metformin, or the combination of melatonin with metformin attenuated the olanzapine-induced adipose deposit tissue growth. The effect was more pronounced for the combination of olanzapine with melatonin and metformin. Because most of the results were not statistically significant we can deduce that in the chronic experiment, adaptive type modifications of the receptors on which both olanzapine and melatonin act can occur.

Urinary tract infection with Klebsiella pneumoniae in Patients with Chronic Kidney Disease.

Study Motivation: After assessing electronic databases of medical scientific literature, we have observed that the interrelation between urinary tract infections (UTIs) and chronic kidney disease (CKD) is poorly studied, especially when UTIs are caused by Klebsiella pneumoniae (K. pneumoniae). MATERIALS AND METHODS: K. pneumoniae was isolated in 14 urine samples from patients with CKD addmited in the Nephrology Department of the County Emergency Clinical Hospital Craiova. The isolated strains were statistically analyzed in the correlation with the different clinical and functional parameters (age, gender, CKD stage, comorbidities, biochemical parameters-serum urea, creatinine, uric acid and blood electrolytes). The degree of K. pneumoniae susceptibility to antibiotics from different pharmacodynamic classes was assessed. RESULTS: UTIs with K. pneumoniae in patients with CKD in the investigated period represented 0.51% from the total admissions in the clinic and 32.60% from cases of UTI. Eleven patients with this type of infection (78.56%) were in stage 4 and 5 CKD, and from them 4 also had diabetes mellitus type 2 (28.57%). We observed an increased level for serum creatinine (100%), blood urea (85.71%), and serum uric acid (45.45%). Two patients died after installation of cardiovascular changes in CKD, at advanced ages and in the presence of urinary infection. Multiple drug resistance occurred in 6 strains of K. pneumoniae correlated with the degree of kidney failure, advanced age, male gender, and diabetes mellitus. CONCLUSIONS: UTI with K. pneumoniae in patients with CKD is the second cause of urinary infection which raises problems of unfavorable evolution of CKD and also the recurrence of UTI with multiple drug resistance in CKD, which may lead to pharmacotherapeutical problems.

In Vitro and In Vivo Evaluation of Different Solid Dosage Forms Containing Captopril.

AIM: Comparison of Captopril generic formulations on the Romanian market with the reference formulation Capoten (Bristol Myers Squibb), in terms of in vitro release kinetics of active substance and in vivo pharmacokinetics. MATERIALS AND METHODS: Dissolution studies were performed using Apparatus 1 (Basket), DT 800H, Erweka, Germany in acidic medium (0.01 N hydrochloric acid) and an agitation speed of 50 rpm. Experiments were run on 12 tablets of each formulation. Quantification of Captopril was achieved by using a spectrophotometric method, λ=205nm. Clinical pharmacokinetics was determined in the frame of four different bioequivalence studies comparing a single dose four different Captopril 50mg generic tablet products to the innovator drug, Capoten 50mg (Bristol Myers Squibb). RESULTS: Different batches of the reference formulations achieved dissolution profiles of the same form and very closed to each other at all dissolution points. Dissolution profiles of the tested formulations shown similar behavior for all references. Two generic formulations achieved a slower release at early dissolution time points, their release being "diffusion controlled", described by law of Higuchi. In vivo, products proved to be bioequivalent, but variability of space distribution and forms of plasma profiles was much bigger than for the in vitro release curves. Due to very rapid in vitro dissolution, a direct Level A in vitro-in vivo correlation was not possible, but, strangely, the fraction absorbed vs. time clearly followed the same Higuchi law. CONCLUSION: All the studied formulations achieved more than 85% dissolution after 15 minutes which means that whatever the values of dissolution metrics f1 and f2, formulations behave like a solution and generally should not have therapeutic equivalence problems. Slower dissolution profiles correlates with in vivo absorption being described by the same square root law of Higuchi which describe diffusion controlled transport phenomena.

The Qsar Study of Azole Derivatives Using Molecular Descriptors for Quantum Molecular States.

Azoles are the main antifungal agents currently used in systemic therapy and local mycoses. The class of azole derivatives has been studied using fingerprint descriptors based on electronegativity of the occupied molecular orbitals (OMO) and unoccupied molecular orbitals (UMO). The Hansch equations that correlates partition coefficient with chemical structure allows us to identify the nature of the atoms involved in ligand (drug) - receptor interactions, as well as the nature of those interactions. The results indicate that in the most reactive molecular states, such as states HOMO and LUMO, the oxygen atoms are actually involved in the interaction of the ligand - receptor by the transfer of electrons from the biological receptor to the oxygen atoms.