Bioequivalence testing of a new tablet formulation of generic fluoxetine.

The pharmacokinetics and relative bioavailability of fluoxetine capsules (reference) and tablets (test) were compared in 24 healthy subjects of both sexes after a single 20 mg oral dose of fluoxetine (as a hydrochloride salt). A randomized, crossover design with a 2-week wash-out period between each dose was applied. Serum samples, obtained before dosing and at various appropriate time points up to 192 hours, were analyzed for fluoxetine and norfluoxetine content by a simple, accurate and precise HPLC method. ANOVA, power analysis, 90% confidence intervals (CI), and two one-sided tests were used for the statistical analysis of pharmacokinetic parameters. The tolerability of the preparations was good. The respective point estimates of the ratios of the geometric means of log-Cmax and log-AUC(0-infinity) of fluoxetine were 0.912 and 0.935 with 90% of 0.838-0.992 and 0.857-1.020. The corresponding point estimates of norfluoxetine were 0.952 (90% CI = 0.843-1.075) and 0.904 (90% CI = 0.807-1.013), respectively. Since both 90% CI for the AUC(0-infinity). and Cmax geometric mean ratios of fluoxetine and norfluoxetine were included in the 80% to 125% interval proposed by the FDA the test drug (fluoxetine tablets) was considered bioequivalent to the reference one (Prozac capsules) according both to the rate and extent of absorption.

Modulatory effects of garlic extracts on proliferation of T-lymphocytes in vitro stimulated with concanavalin A.

Different active components from the garlic (Allium sativum) possess immunomodulatory activity both in vitro and in vivo. However, mechanisms of their actions are not sufficiently elucidated. In this study we examined the effects of garlic aqueous extract (GAE) and garlic ethanolic extract (GEE), prepared from two different garlic powder samples, on proliferation of rat thymocytes and splenocytes in culture, stimulated with concanavalin A (Con A). It has been shown that the extracts from both samples significantly modulate lymphocyte proliferation, triggered by this potent T-cell mitogen, depending on the type and dilutions of extracts and concentrations of Con A. The extracts, alone, were not mitogenic for lymphocytes. Generally, higher concentrations of the extracts showed inhibitory effects, whereas lower concentrations significantly augmented proliferation of lymphocytes. The stimulatory effect of GAE was stronger using splenocytes and suboptimal concentrations of Con A as a consequence of increased interleukin 2 (IL-2) production as well as the expression of IL-2 receptor alpha (IL-2Ralpha). The relationship between these two phenomena was demonstrated using neutralizing anti-IL-2Ralpha monoclonal antibody. The inhibitory effect of GAE correlated with a decrease in IL-2 production, but was not followed by down-regulation of IL-2Ralpha expression. The addition of IL-2 almost completely abolished inhibition of lymphocyte proliferation in the presence of higher concentrations of GAE.

A bioavailability/bioequivalence study of two oral lansoprazole formulations after single administration to healthy volunteers.

Two oral lansoprazole formulations, containing encapsulated microgranules, Lasoprol (test formulation) and Lanzor (reference), were administered to 12 healthy volunteers of both sexes in a single dose of 30 mg lansoprazole in order to investigate their comparative bioavailability. No statistically significant differences, at the probability level of 90%, were observed neither for the maximal serum concentrations (1.12:1.22 micrograms/ml) nor for the area under the concentration-time curves (5.01:5.77 micrograms/ml.h), the parameter to which the inhibition of acid secretion induced by lansoprazole is directly related. The similar holds true for the value of time to reach the maximal concentration of lansoprazole in serum, although this parameter was previously described as less sensitive in comparative bioavailability studies. The terminal elimination half-lives were 4.56 h for Lasoprol and 4.57 h for the reference formulation. The results indicate the bioequivalence and good tolerability of both lansoprazole formulations. The overall pharmacokinetic profile of the drug was comparable with the data previously reported by other investigators.

T-2 toxin affects proliferation of three different neoplastic cell lines.

The antiproliferative effect of T-2 toxin (T-2) towards mouse melanoma B16 cells, human myelogenous leukemia K562 cells, and human cervix carcinoma, HeLa cells, was studied. For the first four days of T-2 presence B16 cell survival was decreased in dose dependent fashion. However, cell survival after eleven days T-2 action may be dual: some stimulation of cell growth that was direct function of the number of seeded cells per well was observed and cell survival (for the highest number of seeded cells) six times greater than control, was noticed at 20 nM T-2 toxin concentration. A smaller cell growth stimulation (cell survival more than 3 times higher than control) was observed with a lower cell number seeded per well. Nevertheless, by eleventh day concentrations of T-2 higher than 35 nM completely inhibited B16 cell proliferation. The same trend was noticed for T-2 action towards K562 cells. Treatment of HeLa cells with various T-2 concentrations led to a marked inhibition of cell survival that was more pronounced at the end of 44th or 72nd hour, than after the 20th hour of agent's action. ICs50 values obtained in the present work, suggest that B16 cells were the most sensitive to T-2 antiproliferative action, while HeLa cells were the most resistant. When PBMC were cultured with HeLa cells the antagonism against various T-2 concentrations was observed; cell survival determined after 44, or 72 hours of cells incubation, was less decreased compared to cultures treated with T-2, or with PBMC only. In addition, it was shown that T-2 and cis-DDP had an antagonist effect on HeLa cells survival.

Oxime-induced reactivation of acetylcholinesterase inhibited by phosphoramidates.

The reaction of human erythrocyte acetylcholinesterase (AChE) with a set of structurally related phosphoramidates was studied in order to investigate the properties of phosphorylated enzyme and the effects of 4 oximes PAM-2, TMB-4, HI-6 and BDB-106 on the reactivation of inhibited AChE. Second-order rate constant of the phosphorylation reaction of the compounds towards the active site of AChE range between 5.0 x 10(2) and 4.9 x 10(6) M-1min-1 and their inhibitory power (I50) was from 7.3 x 10(-5) to 5.7 x 10(-9) M for 20 min incubation at 37 degrees C. The oximes used were weak reactivators of inhibited AChE except for (C4H9O)(NH2)P(O)DCP (DCP, -O-2,5-dichlorphenyl group) and (C6H13O)(NH2)P(O)SCH3 where we have obtained good reactivation. Imidazole oxime BDB-106 proved to be a potent reactivator of tabun-inhibited AChE.

[Determination of albendazole and its main metabolite albendazole sulfoxide in the hydatid fluid of human echinococcal cysts using HPLC]. / Odredivanje albendazola i glavnog metabolita albendazol sulfoksida u hidatidnoj tecnosti ehinokoknih cista ljudi metodom HPLC.

Concentrations of albendazole and its active metabolite in echinococcal cyst of the human liver were determined in order to evaluate drug effects of the decrease of protoscolex vitality. Albendazole concentration of 0-64.9 micrograms/ml and albendazole sulfoxide of 0-40.8 micrograms/ml were found in cysts. The protoscolexes showed markedly manifested morphologic changes up to the disintegration. The postoperative follow up of patients within 24 months discovered no recidives of the disease and the patients were regarded as cured. On the basis of the results obtained it has been concluded that the use of albendazole in the dose of 800 mg/day within 28 day is sufficient for achievement of therapeutic drug level in vivo conditions.