16 month survey of cyclosporine utilization evaluation in allogeneic hematopoietic stem cell transplant recipients

Objectives: Graft versus host disease [GVHD] is a life threatening reaction in the stem cell transplantation process. Nowadays Cyclosporine is the most commonly utilized agent for GVHD prophylaxis and it has a major role in successful transplantation. Cyclosporine has been applied for many years in this field but it could be stated that currently no general consensus is available for its optimal method of administration. Conditions related to cyclosporine administration and possible related adverse reactions observed closely in our patients with the aim of constructing a comprehensive practice guideline in the future

Patients and Methods: Allogeneic stem cell transplant recipients who have been taking cyclosporine were monitored during and after their hospitalization while recording all observations on predefined questionnaires on the basis of periodic clinical and laboratory examinations for a 16 month period

Results: Mean recorded duration of infusions was 1.44 +/- 0.68 h and by twice daily administration, means intravenous and oral dose was 101.85 +/- 22.03 mg and 219.28 +/- 63.9 mg, respectively. A mean CsA trough level after about 12 h of specified unique doses was 223 +/- 65 ng/mL. We found hypertension, nephrotoxicity, neurotoxicity, hypertension, and dyslipidemia in about 14, 20, 48, and 94 percent of patients

Conclusions: This study proposed that permanent guidance of healthcare team according to a fixed and standard method of cyclosporine administration routine with using efficient facilities and protocols would be helpful considerably for an optimal pharmacotherapy

Further stimulation of cellular immune responses through association of HPV-16 E6, E7 and L1 genes in order to produce more effective therapeutic DNA vaccines in cervical cancer model

Cervical cancer has been shown to be highly associated with human papillomavirus [HPV] infection. The viral oncogenes E6 and E7 are constantly expressed by the tumor cells and are therefore potent targets for therapeutic genetic vaccination. In the present study, it was investigated the potential effect of HPV-16 E6, E7 and L1 co-administration to activate specific cytotoxic T lymphocytes in tumor mice models. The HPV-16 E6, E7 and L1 genes from Iranian isolate were separately inserted into the mammalian expression vector, pcDNA3, to construct the DNA vaccine candidates. Tumor-bearing Animals [C57BL/6 mice] were immunized with the vaccine candidate; then, Lymphocyte Proliferation Assay [LPA] and relative tumor volume measurements were carried out in order to examine the immunological effects of the vaccine. Obtained results showed that co-administration of the HPV-16 E6, E7 and L1 DNA induced HPV-16 specific cellular immune responses and also protected against TC-1-induced tumor in vivo compared with negative controls. The results showed that mixed delivery systems might be valuable to improve the magnitude of the induced immune responses and confirmed therapeutic effects of HPV-16 E6, E7 through cytotoxic T lymphocyte induction and illustrate the new promising role for HPV-16 L1 CTL epitopes as a suitable CTL inducer

simple and sensitive HPLC method for fluorescence quantitation of doxorubicin in micro-volume plasma: applications to pharmacokinetic studies in rats

A validated HPLC method was developed to determine the doxorubicin concentration in a small volume of rat plasma [60 microL] with convenient fluorescence detection. Sample preparation includes a simple one-step liquid-liquid extraction using a minimum amount of organic solvent, with extraction recovery more than 95%. The analysis was accomplished using PerfectSil C18 column maintained at 35 [degree]C and a mobile phase consisted of acetonitrile and water [32:68, v/v; pH=2.6]. The flow-rate was kept at 1 mL/min and the column effluent was monitored with a fluorescence detector at an excitation and emission wavelength of 470 and 555 nm, respectively. The detection limit was 5 ng/mL. No analytical interference was observed from endogenous components in the rat plasma. This method was feasibly applied to the pharmacokinetic study of 5 mg/Kg of doxorubicin after the intravenous administration to rats

Preparation and characterization of stable Nanoliposomal formulation of fluoxetine as a potential adjuvant therapy for drug-resistant tumors

Chemotherapy research highly prioritizes overcoming the multidrug resistance [MDR] in human tumors. Liposomal formulation of fluoxetine, as a fourth generation chemosensitizer, was constructed and characterized for percent entrapment, release profile, morphology, particle size, zeta potential and stability. Liposomes were prepared using different active loading techniques. The influence of different formulation variables such as loading methodology, type of main lipid, addition of PEGylated lipid and cholesterol percentage was evaluated to achieve required entrapment efficiency, in vitro release behavior and stability. The studied parameters had significant effect on physicochemical characteristics of the nanocarriers. High fluoxetine encapsulation efficiency [83% +/- 3%] and appropriate particle size [101 +/- 12 nm] and zeta potential [-9 +/- 2 mv] were achieved for PEGylation liposomes composed of DSPE-PEG, DSPC and cholesterol at respective molar ratio of 5:70:25. An in vitro fluoxetine release of about 20% in 48 h was observed from optimum formulation. Atomic force microscopy [AFM] studies confirmed homogeneous distribution of particles and spherical shape with smooth surface. The optimum formulation was stable for 9 days when incubated at 37 [degree sign]C. The results of this study are very encouraging for application of the developed fluoxetine liposomal formulation in drug-resistant tumor models

effect of PEG molecular weights on dissolution behavior of simvastatin in solid dispersions

The purpose of the present study was to investigate the effect of polyethylene glycol [PEG] molecular weights [6000, 12000 and 20000] as solid dispersion [SD] carriers on the dissolution behavior of simvastatin. SDs with various drugs: carrier ratios were prepared by solvent method and evaluated for dissolution rate. Differential scanning calorimetry [DSC], X-ray diffraction [XRD], infrared spectroscopy and solubility studies were also performed on the optimum SD formulation. Samples prepared with all three types of PEG showed improved drug dissolution compared to intact drug and corresponding physical mixtures. Meanwhile, the best result was obtained by PEG 12000 with drug: carrier ratio of 1:7 which showed a 3-fold increase in dissolution rate compared to the intact drug. Based on DSC and XRD, no crystalline change occurred during the sample preparation. Solubility studies revealed that increasing the PEG molecular weight resulted in higher phase solubility of drug. In addition, saturated solubility of the optimum SD was significantly higher than that of intact drug and the related physical mixture [24.83, 8.74 and 8.88 microg/mL, respectively] that could be due to the decreased particle size and aggregation. The results confirmed the influence of PEG molecular weight on drug dissolution rate from solid dispersion systems

Enhanced permeability of etoposide across everted sacs of rat small intestine by vitamin E-TPGS

Etoposide, a widely used anticancer drug, exhibits low and variable oral bioavailability mainly because of being substrate for the efflux transporter, P-glycoprotein [P-gp]. Therefore, the present study was aimed to investigate the effect of D-alpha-tocopherol polyethylene glycol 1000 succinate [TPGS] and PEG 400 as P-gp inhibitors on the intestinal absorption of etoposide. Everted sacs of rat small intestine were incubated in Krebs buffer solution which contained etoposide in the absence or presence of various concentrations of TPGS or PEG 400. The effect of verapamil as a known P-gp inhibitor on the absorption of drug was also studied

The absorptive transport of etoposide was significantly enhanced [p < 0.001] in the presence of verapamil [100 [micro]g/mL] and TPGS [over the concentration range of 0.002-0.1 mg/mL], suggesting that the inhibition of P-gp located in the intestine may be involved in the enhancement of etoposide absorption. However, the addition of PEG 400 at various concentrations [0.05, 0.1 and 0.5% w/v] had no effect on the etoposide transport. No significant difference was found between the permeability values in the absence and presence of the maximum concentration of TPGS for two transport markers, lucifer yellow and imipramine, indicating that the enhancement in etoposide permeability in the presence of TPGS was not due to the compromise in tight junctions or membrane integrity of epithelial cells

The results of the study suggest that the use of TPGS as a safe excipient in etoposide formulations may enhance the oral bioavailability of etoposide and result in a predictable oral absorption

effect of various surfactatnts on release behavior of procainamide HCL from ethylcellulose based matrices

The effect of different kinds of surfactants in various concentrations incorporated in an inert matrix, on the release of procainamide hydrochloride, as a cationic model compound, was investigated in this study. Sodium lauryl sulfate and sodium stearate as anionic surfactants, cetyl pyridinium chloride and cetyltrimethyl ammonium bromide as cationic and span 60 and tween 80 as non-ionic surfactants were selected. Hydrophobic matrices were prepared using procainamide HCl, ethyl cellulose, dicalcium phosphate and different percentages of each surfactant and the dissolution rate of drug from various matrices was determined in pH values1.2 [for 2 h] and 7.2 [up to 10 h]. The results showed that incorporation of anionic surfactants in matrix preparations resulted in a remarkable decrease in the release rate of procainamide HCl [P < 0.05], which was attributed to the formation of a poorly soluble complex between the cationic drug and the anionic surfactant. The formation of complex was confirmed by the precipitation titration test. On the other hand, presence of cationic surfactants considerably increased the drug release rate and it was noted that by raising the percentage of surfactant, a faster drug release rate release was achieved. With span 60 there was no change in drug release rate, probably due to its lower wetting capability. While in the case of tween 80, as a hydrophilic non-ionic surfactant, the drug release rate was increased, although statistically not significant. In general, it seems that the influence of cationic and non-ionic surfactants on drug release rate was in accordance with the ability of each surfactant in wetting the matrices and producing a greater number of channels for the dissolution fluid to leach out the drug. Kinetics evaluation of the release profiles showed that the Higuchi equation is the main model, fitting the data

[Determination of radiation dose rates and urinary activity of patients received Sodium Iodide-131 for treatment of differentiated thyroid carcinoma]

Sodium Iodide-131 is administrated for treatment of hyperthyroidism and thyroid cancer. Iodine-131 has multiple routs of excretion [Urine, saliva, sweat, milk, feces, exhalation] from the body. Patients receiving Sodium Iodide-131 therapy exposes other persons and the environment to unwanted radiation and contamination. The major source of radiation dose from administration of Iodine-131 is external radiation, also there is a potential for exposure via contamination. Precautions are necessary to limit the radiation dose to family members, nursing staff and members of public and waste treatment workers to less than 1mSv. Patients received Sodium Iodide-131 may come into close contact with other persons. In order to derive appropriate recommendations, dose rates were measured from the anterior mid-trunk of 29 patients in the upright position within 15 minutes post-dose administration at 3 meters and just before they left the nuclear medicine department at 0.5, 1 and 3 meters. We have also measured urinary iodide excretion in 29 patients to estimate Sodium Iodide-131 urinary excretion pattern in Iranian patients. Based on results, the maximum cumulative dose to nursing staff was on third day [Leaving day] still less than recommended dose by ICRP. The cumulative dose of family members will be more but regarding the time and distance in close contact it will also be less than recommended dose by ICRP. Radiation dose rate was decreased significantly on third day. The urinary excretion patterns in all patients were similar. The urinary excretion rate-time curve in all patients showed multiple peaks due to retention and redistribution of Iodine-131 or entrohepatic cycle of radioiodinated thyroid hormones, which didn't allow calculation of urinary excretion rate constant. The results also showed that 67 hours post administration of Sodium Iodide-131 about 70% of radiopharmaceutical was excreted through urine, 28% physically decayed or eliminated through other biological routes

Pharmacokinetics and comparative bioavailability of two diltiazem tablet formulations healthy volunteers

The pharmacokinetic parameters and bioavailability of diltiazem following a single oral administration of a generic diltiazem 60 mg tablet [Sobhan Pharmaceuticals, Iran] were compared to those of a reference product [Entrydil, Orion Pharmaceuticals, Finland]. Twelve healthy male volunteers received a single oral dose of either formulation following overnight fasting in a double blind, randomized, crossover study. Blood samples were collected at selected times during 24 h and diltiazem plasma concentrations were determined with a sensitive HPLC method. Individual pharmacokinetic parameters, t1/2, t1/2[abs], K, Ka, Tmax, Cmax, Vd/F, Cl/F, AUC0-24 and AUC0-