Ofloxacin pharmacokinetics in saliva

Objective: To study the pharmacokinetics of ofloxacin using salivary drug concentration when administered alone or in combination with rifampicin (R), isoniazid (H) and pyrazinamide (Z) and also to assess the saliva to plasma concentration ratio. Material and Methods: Twelve healthy male volunteers were investigated on four different occasions with an interval of at least one week between occasions. They were administered ofloxacin, either alone or in combination with R, H and Z. A partially balanced incomplete block design was adopted and the subjects were randomly allocated to each group. Salivary and plasma concentrations of ofloxacin were measured at 1, 2, 3, 6 and 8 h after drug(s) administration using validated methods. Results: There were no significant differences between various pharmacokinetic parameters when ofloxacin was administered alone or in combination with R, H and Z. The mean saliva to plasma ratio of ofloxacin concentration was around 0.6. The bioavailability indices of ofloxacin in the saliva and plasma were similar in all the groups. Conclusion: Several pharmacokinetic parameters could be calculated using salivary concentrations of ofloxacin. The determination of ofloxacin levels in saliva may be useful in therapeutic drug monitoring and pharmacokinetic studies

Use of stable isotopes, organic and inorganic chemistry to identify pollution sources and weathering processes in two small tropical rivers in southwestern India

The two main objectives of this study were to assess pollution dynamic from organic and inorganic major ion chemistry and stable isotopes (δ15N and δ18O) and to determine the weathering processes using carbon isotopes in two tropical river basins, i.e. Nethravati and Swarna, along southwest coast of India. These short length river basins (around 100 km) are characterized by high annual rainfall, warm temperature, high runo" (~3300mm) draining Precambrian basement rocks composed of green-stones, granitic-gneiss, charnockite and meta sediments. Intense silicate weathering is induced by high runo" and warm temperature (Gurumurthy et al., 2012). In this study, stable isotopes (δ15N & δ18O)of organic molecules from sewage and agricultural effluents,and carbon isotopes (δ13C) of dissolved organic carbon (DOC) and dissolved inorganic carbon (DIC) were measured to trace agricultural and domestic pollution and to identify the sources of inorganic carbon and the nature of chemical weathering in these river basins. Carbon isotopes measured on DIC reveals sources of carbon into the river, such as carbonate/silicate weathering of rocks, mineralization of organic matter from C3/C4 plants, soil and atmospheric CO2. The nitrate and phosphate levels remain low, with values ranging from 5 to 9 μM, and 0 to 2 μM respectively. The δ13C DIC values range from =-9.03 +/- 0.99 for the Swarna basin to -8.08 +/-0.78 for the Nethravati basin. These values point to a mixing of carbonate and silicate weathering products with a dominance of C3 vegetation, prevalent in the Western Ghats. The DOC values for both river basins are very low and very close: 0.72 +/- 0.09 mg/L (Swarna river) and 0.62 +/-0.11 mg/L (Nethravati river). This indicates that the contributions of organic matter from the adjacent forests and the $ood plains are very low during the sampling period. The analysis of organic acids reveals low amount of Oxalate and Acetate, and trace of Malate and Tartaric acids. The dissolved and particulate organic carbon (DOC and POC) concentrations are very low in these two rivers. During the dry season, river discharge is mainly supplied by groundwater with generally low contents in dissolved and particulate fractions. Even if we observe low concentration, we measured higher DOC and POC in the Swarna river. These higher DOC concentrations are accompanied with lower SUVA value. This indicates that more labile DOC (less aromaticity) is exported within this basin during dry season. C/N values in POC also show that the organic carbon is “fresher” and is probably more autochtonous than in the Nethravati river. Indeed, C/N value are closer of an autochthonous production (C/N : 2-6) than allochthonous one (C/N: 8-20). These observations can be explained as the Svarna watershed land use is more agricultural than in Nethravati. Agricultural lands generally export signi%cant amount of nutrients to rivers and participate to enhance autochthonous productivity. Autochthonous organic carbon production is more labile and less aromatic

Dose related pharmacokinetics of ofloxacin in healthy volunteers

OBJECTIVE: To evaluate the pharmacokinetic profile of ofloxacin in healthy volunteers after single oral doses of 600 and 800 mg. DESIGN: Seven healthy volunteers were administered 600 and 800 mg of ofloxacin on two occasions with an interval of one week. Paired samples of blood and saliva were collected after 1, 2, 3, 6, 9, 12, 24, 32 and 48 hours post-dose. Urine samples were collected over a period of 0–6, 6–12 and 12–24 hours. Concentrations of ofloxacin in plasma, saliva and urine were assayed by high performance liquid chromatography. RESULTS: Increases of 22% in peak plasma concentration (Cmax) and 40% in area under the concentrationtime curve (AUC0–24) were observed with the 800 mg dose. The other parameters, namely time to attain Cmax, half-life, the apparent volume of distribution, plasma and renal clearance and percentage of dose excreted in urine over 24 hours were independent of doses. The mean ratios of the concentration in saliva to the concentration in plasma ranged from 0.4–0.6, and the correlation coefficient was 0.94. CONCLUSIONS: Dose proportionality was observed in Cmax and AUC0–24 when 600 and 800 mg doses of ofloxacin were given. Ofloxacin determined in saliva seems to be suitable for therapeutic drug monitoring

Pregnancy associated plasma protein-A (PAPP-A) as an early marker for the diagnosis of acute coronary syndrome.

Aims and objectives Pregnancy associated plasma protein-A (PAPP-A), a metalloproteinase plays a pivotal role in the pathogenesis of atherosclerosis. Recent studies have reported that elevated levels of PAPP-A, signal the onset of acute coronary syndrome (ACS). We, therefore, proposed to study the analytical competence of PAPP-A in patients admitted to the emergency department with chest pain and finally diagnosed as ACS. Methods and results Pregnancy associated plasma protein-A was measured using enzyme-linked immunosorbent assay (ELISA) in 485 patients admitted to emergency care unit, of which 89 patients were diagnosed as Non-cardiac chest pain (NCCP). Elevated levels of PAPP-A were observed in patients diagnosed as ACS on comparison with the controls. Receiver operator characteristic (ROC) curve analysis showed PAPP-A to be a good discriminator between ischaemic and non-ischaemic patients. The area under the curve was found to be 0.904, 95% CI (0.874–0.929) with 90% sensitivity and 85% specificity (P< 0.0001). The cut-off value from the ROC curve was 0.55 μg/mL above which PAPP-A was considered to be positive. Conclusion Pregnancy associated plasma protein-A seems to be a promising biomarker for identification and risk stratification for patients with ACS

Standardization of the method for estimation of ethambutol in pharmaceutical preparations and biological fluid

A simple column chromatographic method for determination of ethambutol (EMB) in pharmaceutical preparations containing EMB in combination with other anti-TB drugs is presented. The method involved extraction of EMB into an organic solvent. followed by basification and column chromatographic separation on Amberlite CG 50 (100-200 mesh) and elution with suitable eluants and estimation at a wavelength of 270 nm. The assay was linear from 25 to 400 μg/ml. The relative standard deviations of intra and inter day assays were lower than 5%. Ethambutol was recovered from human urine quantitatively and stable for a period of atleast one week in urine stored at-20°C

Simple spectrofluorimetric and microbiological assay methods for the estimation of ofloxacin in biological fluids

Objective: To evolve simple methods for the assay of ofloxacin in biological fluids. Methods: Simple methods for the estimation of ofloxacin in plasma, saliva and urine employing microbiological assay using plate diffusion technique and by fluorimetric method based on the measurement of native fluorescence emitted by ofloxacin, have been described. Results: The recovery of ofloxacin from all the three biologial fluids was 93-98% and the sensitivity was 0.5 μg/ml on all 5 different occasions by both the methods. Anti-TB drugs viz., rifampicin, ethambutol, isoniazid and pyrazinamide and also anti-leprosy drugs viz., dapsone and clofazimine at concentrations of 10 and 20 μg/ml did not interfere with the estimation of ofloxacin by either method. Ofloxacin is stable in biological fluids for a period of at least 8 days at -20°C. Conclusion: Both the methods described are simple, involve very few steps and do not need either costly chemicals or sophisticated equipments

Assay of ethambutol in pharmaceutical preparations

Ethambutol tablets of 200 and 400 mg denominations were assayed by the standard non-aqueous titration method and a simpler calorimetric method. With the titrimetric method, assay values, appreciably higher than the stated content (117% or more), were obtained with the products of 4 companies, while all the values were within 6% of the stated content by the calorimetric method. Rifampicin and pyrazinamide interfered with the estimation of ethambutol by both methods: isoniazid, however, caused an overestimation with the titrimetric method only

Bioavailability of rifampicin following concomitant administration of ethambutol or isoniazid or pyrazinamide or a combination of the three drugs

Background & Objectives: Poor bioavailability of rifampicin (R) in combination with other anti-tuberculosis drugs such as isoniazid (H), pyrazinamide (Z), and ethambutol (E) is a subject of much concern for the last few decades. This could be due to an interaction between R and other drugs. An investigation was therefore undertaken to examine the bioavailability of R in the presence of H, Z and E or a combination of the three drugs. Methods: The study included eight healthy volunteers, each being investigated on four occasions at weekly intervals once with R alone and with three of the four combinations on the three remaining occasions. A partially balanced incomplete block design was employed and the allocation of R or the drug combinations was random. Plasma concentrations of R at intervals upto 12 h were determined by microbiological assay using Staphylococcus aureus as the test organism. The proportion (%) dose of R as R plus desacetyl R (DR) in urine excreted over the periods 0-8 and 8-12 h was also determined. Bioavailability was expressed as an index (BI) of area under time concentration curve (AUC) calculated from the plasma concentrations or proportion of dose of R excreted as R plus DR in urine with the combinations to that with R alone. Results: The bioavailability indices based on AUC were 0.96 with RE, 0.76 with RH, 1.08 with RZ and 0.65 with REHZ. The indices based on urine estimations (0-8 h) were similar, the values being 0.94, 0.84, 0.94 and 0.75, respectively. A second investigation revealed that the decrease of bioavailability of R with H was not due to the excipients present in H tablets. Interpretation & conclusion: Isoniazid alone or in combination with E and Z reduces the bioavailability of R. Urinary excretion data offer a simple and non invasive method for the assessment of bioavailability of R

The Pharmacokinetics of ofloxacin, rifampicin, isoniazid and pyrazinmide when administered alone and in combination

The present study assesses the bioavailability of Ofloxacin (O) following single oral administration of the drug along with Rifampicin (R), or Isoniazid (H), or Pyrazinamide (Z) or a combination of three drugs. Information on the pharmacokinetics of O in the presence of R, H and Z based on the blood concentrations upto 8 hours, on the proportions of the doses of the drugs and their metabolites excreted in urine upto 8 hours and also the effect of O on the other antituberculosis (TB) drugs in terms of absorption and interactions are extensively studied. The bioavailability indices of these drugs are assessed. The investigation was undertaken in a total of 12 male healthy volunteers and each volunteer was investigated on four different occasions at weekly intervals. A partially balanced incomplete block design was employed and the allocation of O or the drug combinations was at random. Plasma concentrations of O, R, H and Z were determined. Urinary excretion of these drugs, together with their primary metabolites was also determined. Various pharmacokinetic parameters were calculated. The results have shown that the bioavailability of O is not impaired when administered with other antituberculosis drugs like R, H and Z and does not exercise any therapeutic penalty. The bioavailability of other anti-TB drugs like R, H and Z does not get affected when administered along with O. Human bioavailability studies, in general, provide direct straightforward information on the degree of absorption and biotransformation of drugs. The results of the present study indicate that the pharmacokinetic properties of O, R, H and Z as assessed after individual and combined administration of these drugs do not get affected or altered. Since there are no interactions among these drugs, the use of 0 in the treatment of pulmonary tuberculosis is justified

A transgenic pig model expressing a CMV-ZsGreen1 reporter across an extensive array of tissues.

Since genetic engineering of pigs can benefit both biomedicine and agriculture, selecting a suitable gene promoter is critically important. The cytomegalovirus (CMV) promoter, which can robustly drive ubiquitous transgene expression, is commonly used at present, yet recent reports suggest tissue-specific activity in the pig. The objective of this study was to quantify ZsGreen1 protein (in lieu of CMV promoter activity) in tissues from pigs harboring a CMV-ZsGreen1 transgene with a single integration site. Tissue samples