The comparative pharmacokinetics of ceftriaxone in the blood and bronchial secretion in patients with different durations in the course of chronic bronchitis

The study on ceftriaxone penetration into bronchial secretion showed that in patients with a short-term history of chronic bronchitis (no more than 3 years) ceftriaxone used in a dose of 1 g once a day intramuscularly was detectable in the bronchial secretion within 10 hours after the administration, its concentrations being 0.67-2.41 micrograms/ml in 3 hours, 15.87 micrograms/ml in 4.5 hours, 4.58 micrograms/ml in 6.5 hours and 2.29 micrograms/ml in 10 hours. In patients with a long-term history of chronic bronchitis (mean 10 to 20 years) the presence of ceftriaxone in the bronchial secretion was detectable in a concentration of 0.51-3.75 micrograms/ml only in 2 hours after its administration. Beginning from the 5th hour after the administration its detection failed. This is indicative of lower ceftriaxone penetration into the bronchial secretion of such patients. The duration of chronic bronchitis did not influence ceftriaxone pharmacokinetics in blood. The contents of the antibiotic in serum and bronchial secretion were determined by HPLC (the resolving power of 0.5 micrograms/ml).     

Treatment of endophthalmitis with a single intravitreous administration of cefotaxime and gentamicin in an experiment]

Experimental endophthalmitis was treated with single intravitreous administrations of cefotaxime (claforan) and gentamicin. It was found that a single administration of cefotaxime to the vitreous body prevented development of endophthalmitis in rabbits previously infected with Staphylococcus aureus, E. coli and Pseudomonas aeruginosa. Vitrectomy in the treatment of endophthalmitis was shown to be promising and provide satisfactory anatomical and functional results.     

Results of utilization of intermittent normobaric hypoxia in patients with bronchial asthma and chronic obstructive bronchitis]

The results of intermittent normobaric hypoxytherapy in 42 patients with bronchial asthma (BA) and 14 patients with chronic obstructive bronchitis (COB) are analyzed. The positive effect is obtained in 76% of patients with BA and 92.8% of patients with COB. In the group of patients with BA the best effect was achieved for atopic form of BA--in 90% of patients, the effect was less pronounced for infection-allergic form--in 73.9% and for mixed form of BA--in 66.7%. In the process of treatment the attacks of asphyxia disappeared or became more occasional in 60.7% of patients; in 32.1% the attacks were more easily arrested or stopped independently; 33.8% of patients decreased doses of constantly taken drugs; in 33% cough ceased or decreased, sputum became to expectorate better; in 41% of patients dyspnea disappeared and considerably decreased. Improvement of the state in 54% of patients was retained for one year and more, in 29%--for 6 months, in 16.6%--for 3-4 months. The course of treatment consisted of 20-25 sessions. The patients breathed in hypoxic gas mixture containing 10% of oxygen (HGM-10) under intermittent conditions alternating with respiration of free air.     

Glycosaminoglycans in the bronchial mucus of patients with chronic bronchitis and mucoid impaction of the bronchus

Glycosaminoglycans were isolated from mucus of patients with chronic bronchitis and mucoid impaction of the bronchus, whose contents were approximately 56 mumoles and 80 mumoles of hexosamine per g of dry weight of mucus respectively. Electrophoretic and chemical characterization and enzymatic susceptibility demonstrated that the glycosaminoglycans in mucus from both groups of the patients contained hyaluronic acid as the main constituent, with undersulphated chondroitin as a minor component. In addition, in mucus from the patient with mucoid impaction of the bronchus chondroitin sulphate and heparan sulphate or heparan sulphate-like substance were identified.     

Evaluation of 24-hour growth hormone spontaneous secretion: comparison with a nocturnal and diurnal 12-hour study

Spontaneous growth hormone (GH) secretion in 116 short children was studied by sampling blood for GH measurement every 20 min over 24 h. We calculated 24-h mean GH concentration (MGHC), diurnal 12-h MGHC (dMGHC) and nocturnal 12-h MGHC (nMGHC). The children were subdivided into four groups: prepubertal children with 'classical' GH deficiency (group 1, n = 12, low responses to two provocative stimuli tests and MGHC less than 3 ng/ml), prepubertal children with 'nonclassical' GH deficiency (group 2, n = 36, normal GH responses to two provocative tests and MGHC less than 3 ng/ml), short normal children (normal GH responses to two provocative tests and MGHC greater than 3 ng/ml) at stage P1 of puberty (group 3, n = 41) and at stage P2 of puberty (group 4, n = 27). The values of MGHC, dMGHC and nMGHC were significantly higher in groups 3 and 4 than in groups 1 and 2, and in group 4 than in group 3. The values of MGHC and nMGHC were significantly higher in group 2 than in group 1. MGHC correlated highly with nMGHC and dMGHC (r = 0.97 and 0.94, respectively; p less than 0.001). On the basis of regression equations between MGHC and nMGHC or dMGHC, the study of the diagnostic accuracy showed values higher for nMGHC than for dMGHC: 94.1 vs. 89.6% for sensitivity, and 93.7 vs. 89.7% for specificity, respectively.     

24-hour temporal pattern of NTPDase and 5'-nucleotidase enzymes in rat blood serum

Circadian rhythms represent an important mechanism to prepare the organism for environmental variations. ATP, ADP, AMP, and adenosine can act as extracellular messengers in a range of biological processes and are metabolized by a number of enzymes, including NTPDases and 5'-nucleotidase. In the present study the authors report that ATPase and ADPase activities present 24-h temporal variations that peak during dark (activity) span. These findings suggest that this enzymatic temporal pattern in blood serum might be important for the normal physiology and function of the organism through the maintenance of extracellular nucleotides at physiological levels.     

Pharmacokinetic investigation of dose proportionality with a 24-hour controlled-release formulation of hydromorphone

Background

The purpose of this study was investigate the dose proportionality of a novel, once-daily, controlled-release formulation of hydromorphone that utilizes the OROS^® Push-Pull? osmotic pump technology.

Methods

In an open-label, four-way, crossover study, 32 healthy volunteers were randomized to receive a single dose of OROS^® hydromorphone 8, 16, 32, and 64 mg, with a 7-day washout period between treatments. Opioid antagonism was provided by three or four doses of naltrexone 50 mg, given at 12-hour intervals pre- and post-OROS^® hydromorphone dosing. Plasma samples for pharmacokinetic analysis were collected pre-dose and at regular intervals up to 48 hours post-dose (72 hours for the 64-mg dose), and were assayed for hydromorphone concentration to determine peak plasma concentration (C_max), time at which peak plasma concentration was observed (T_max), terminal half-life (t_1/2), and area under the concentration-time curve for zero to time t (AUC_0-t) and zero to infinity (AUC_0–∞). An analysis of variance (ANOVA) model on untransformed and dose-normalized data for AUC_0-t, AUC_0–∞, and C_max was used to establish dose linearity and proportionality.

Results

The study was completed by 31 of 32 subjects. Median T_max (12.0–16.0 hours) and mean t_1/2 (10.6–11.0 hours) were found to be independent of dose. Regression analyses of C_max, AUC_0–48, and AUC_0–∞ by dose indicated that the relationship was linear (slope, P ≤ 0.05) and that the intercept did not differ significantly from zero (P > 0.05). Similar analyses with dose-normalized parameters also indicated that the slope did not differ significantly from zero (P > 0.05).

Conclusion

The pharmacokinetics of OROS^® hydromorphone are linear and dose proportional for the 8, 16, 32, and 64 mg doses.

Trial Registration

Clinical Trials.gov NCT00398957

     

Cytological and biochemical indices of induced sputum in patients with bronchial asthma and chronic obstructive bronchitis

The aim of our research was to study the apoptotic index and the representativeness of CD95-receptor in the effector cells, in addition to estimation of the content of tumor necrosis factor-alpha in the induced sputum supernatant observed in patients with bronchial asthma and chronic obstructive bronchitis. These indices were evaluated in the disease dynamics and involves various treatment programs. The object of our research was induced sputum. The analysis has proven that apoptotic index of effector cell nuclei, representativeness of CD95-receptor and the content of tumor necrosis factor-alpha in the induced sputum differed, respectively, in patients with bronchial asthma and chronical obstructive bronchitis, and depended on the period of disease and employed treatment. The induced sputum analysis results can be used for the airway inflammation activity monitoring, with regard to these diseases and to treatment efficiency monitoring.     

Liquid chromatographic determination of the plasma concentrations of cefotaxime and desacetylcefotaxime in plasma of critically ill patients

A method for the simultaneous determination of cefotaxime (CTX) and desacetylcefotaxime (DES) in plasma was developed, using acetonitrile protein precipitation and high-performance liquid chromatography (HPLC) with UV-detection at 285 nm. Desacetylcefotaxime was also analysed after conversion in highly acidic medium to its lactone form (DES-lactone). The chromatographic separation was performed on a C18 Aqua column. The lower limit of quantitation was 1 microg/ml for CTX and 0.5 microg/ml for DES and DES-lactone, using 25 microl of plasma samples. The linearity of the calibration curves was satisfactory as indicated by correlation coefficients of > or =0.990. The within-day and between-day precisions were <12% (n = 18) for the two products and the accuracy was between 88 and 101%. The developed HPLC method was applied for CTX and DES determination in plasma samples of critically ill patients after continuous intravenous infusion of CTX.