Ceftazidime: pharmacokinetics in young volunteers versus elderly patients and therapeutic efficacy with complicated urinary tract infections

Thirty-six urological patients (21 male, 15 female) aged 21 to 83 years with complicated and/or hospital-acquired urinary tract infections due to sensitive bacteria were treated with ceftazidime intravenously with a daily dose of 2 g bd over 5 to 17 days. Twenty-seven patients were followed for 1 to 4 weeks after therapy. Cure was observed in 41%, reinfection in 33% and relapse in 26% of the patients. Eradication of the original pathogen occurred in 74%. Five patients showed minor side effects: diarrhoea (2), nausea (1), rash (1), headache (1). No signs of renal, hepatic or haematological toxicity were observed. A pharmacokinetic study was performed in 13 elderly patients aged 63 to 83 years on day 1 of treatment and in 6 volunteers aged 24 to 32 years following administration of 2 g of ceftazidime as short intravenous infusion. The mean serum half life in 12 patients 2.9 h significantly higher than in volunteers (1.75 h). Serum concentrations in patients on day 7 of treatment, however, showed no accumulation when treated with a dosage of 2 g bd

Pharmacokinetics, in-vitro activity, therapeutic efficacy and clinical safety of aztreonam vs. cefotaxime in the treatment of complicated urinary tract infections

The minimal inhibitory concentrations (MICs) of aztreonam and cefotaxime were determined against 400 isolates from urological in-patients with complicated and/or hospital acquired urinary tract infections (UTI). Against the Gram-negative rods the activities of both antibiotics were comparable except for higher activity of aztreonam against Pseudomonas aeruginosa. The pharmacokinetic study in nine elderly patients showed a prolonged plasma half life of aztreonam (2.7 h) as compared to younger volunteers (1.6-1.9 h). In a prospective randomized study 39 urological patients with complicated and/or hospital acquired UTI were treated with 1 g aztreonam or cefotaxime iv twice daily for 4 to 15 days. Cure was obtained in 5 out of 18 patients in the aztreonam and 7 out of 20 patients in the cefotaxime group. There were 3 superinfections, 7 relapses and 3 reinfections in the aztreonam group and 1 failure, 1 superinfection, 6 relapses and 5 reinfections in the cefotaxime group. There was no significant difference in therapeutic efficacy between the two antibiotics. Both antibiotics were tolerated well and seem to be equally effective in the treatment of complicated UTI caused by sensitive organisms

High-performance liquid chromatography analysis of mezlocillin, piperacillin, their degradation products, and of ioxitalamic acid in plasma and urine of healthy volunteers

In plasma and urine of 10 healthy volunteers after intravenous administration of 4 g mezlocillin and piperacillin, respectively, the parent compounds as well as degradation products were assayed by high-performance liquid chromatography. Ioxitalamic acid, a renal contrast medium, was administered simultaneously, in order to measure the glomerular filtration rate, and to control the collection of 24-h urine. As metabolite of mezlocillin the corresponding penicilloic acid only was found, whereas in the case of piperacillin a further degradation product was observed. Half of the doses given was recovered in the urine as unchanged drugs, and in addition 5-10% as metabolites. No differences were found in the pharmacokinetic behaviour of both antibiotics

Strukturelle Charakterisierung eines unbekannten Metaboliten von Ciprofloxacin [Structural characterization of an unknown metabolite of ciprofloxacin]

The chemical structure of an unknown metabolite of ciprofloxacin (CAS 85721-33-1) is characterized by means of reversed phase ion pair liquid chromatography, absorption and fluorescence spectroscopy, partition coefficients as well as chemical and enzymatic hydrolytic degradation. A chemical structure of the unknown metabolite is proposed: N-formyl-desethylen-ciprofloxacin. It can be formed as an intermediate in the oxidative degradation of ciprofloxacin via oxociprofloxacin to desethylen-ciprofloxacin, or it may be formed by conjugation of desethylen-ciprofloxacin with formic acid. The amounts found in plasma and urine of patients were in the range of desethylen-ciprofloxacin, i.e. about 1% of the parent compound

Emission of exoelectrons during oxidation of Cs via thermal activation of a metastable O^-₂ surface species

Exposure of Cs surfaces to O2 causes the emission of exoelectrons. With a Cs monolayer on Ru(0001) the maximum yield is observed with an already partly oxidized surface on which a metastable O-2 species could be identified. Thermally activated transformation (with an activation energy of 0.8 eV) of this phase leads to dissociation accompanied by exoelectron emission via Auger deexcitation

Mitochondrial and Cellular Function in Fibroblasts, Induced Neurons, and Astrocytes Derived from Case Study Patients: Insights into Major Depression as a Mitochondria-Associated Disease

The link between mitochondria and major depressive disorder (MDD) is increasingly evident, underscored both by mitochondria’s involvement in many mechanisms identified in depression and the high prevalence of MDD in individuals with mitochondrial disorders. Mitochondrial functions and energy metabolism are increasingly considered to be involved in MDD’s pathogenesis. This study focused on cellular and mitochondrial (dys)function in two atypical cases: an antidepressant non-responding MDD patient (“Non-R”) and another with an unexplained mitochondrial disorder (“Mito”). Skin biopsies from these patients and controls were used to generate various cell types, including astrocytes and neurons, and cellular and mitochondrial functions were analyzed. Similarities were observed between the Mito patient and a broader MDD cohort, including decreased respiration and mitochondrial function. Conversely, the Non-R patient exhibited increased respiratory rates, mitochondrial calcium, and resting membrane potential. In conclusion, the Non-R patient’s data offered a new perspective on MDD, suggesting a detrimental imbalance in mitochondrial and cellular processes, rather than simply reduced functions. Meanwhile, the Mito patient’s data revealed the extensive effects of mitochondrial dysfunctions on cellular functions, potentially highlighting new MDD-associated impairments. Together, these case studies enhance our comprehension of MDD

Pharmacokinetic parameters and haemodynamic actions of midodrine in young volunteers

In two groups of volunteers pharmacological parameters of the antihypotensive drug midodrine have been investigated. The first group of 12 male healthy volunteers received 2.5 mg midodrine hydrochloride intravenously, as drinking solution or as tablet according to a randomized cross-over design. Plasma and urine samples were analyzed for midodrine and its main metabolite ST 1059 by high-performance liquid chromatography. The mean maximum concentration in plasma for midodrine was 10 ng/ml 20-30 min after oral administration, for ST 1059 5 ng/ml after 1 h. Midodrine was eliminated with a terminal half-life of 0.5 h, ST 1059 with a half-life of 3 hrs. The mean area under the plasma-level vs. time curve (AUC) of ST 1059 after administration of 2.5 mg midodrine i.v. was 28.7 ng x h/ml, and similar for the other formulations which are considered to be bioequivalent. In a second group of 15 volunteers with postural hypotension midodrine (M) as alpha-sympathomimetic drug and oxilofrine (O) as beta-sympathomimetic drug was given i.v. in a randomized double blind study against placebo (P). Blood pressure (BP), heart rate (HR) and circulating catecholamines (CA) were determined before and after injections of the drugs as well as before and during 10 min of tilting. Echocardiographic parameters were obtained at rest before and after the administration of the drugs. Blood pressure remained unchanged at rest and during orthostasis after all agents injected. After oral administration of midodrine heart rate was decreased and systolic blood pressure increased significantly and dose-dependently. M lowered circulating noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS

Circulating and tissue catecholamines in rats with chronic neurogenic hypertension

To study the role of peripheral catecholamines in plasma and different tissues in neurogenic hypertension we measured directly blood pressure, maximum rate of left ventricular pressure rise (dp/dtmax) and heart rate through an aortic catheter 5 weeks after total sino-aortic baroreceptor deafferentation in male Sprague-Dawley rats. Blood samples were collected through the same catheter to determine plasma catecholamine concentrations. Blood pressure and dp/dtmax were significantly higher in neurogenic-hypertensive rats when compared with sham operated rats. Plasma noradrenaline concentrations and plasma adrenaline concentrations reached significantly higher levels in neurogenic-hypertensive rats. In the heart noradrenaline content was lower (when calculated per g wet weight) and in the adrenal medulla adrenaline content was higher in neurogenic-hypertensive rats, when compared with sham operated controls. A significant positive correlation was found between dp/dtmax and plasma noradrenaline concentrations. It is concluded that sino-aortic baroreceptor deafferentation produces a significant chronic hypertension, probably supported by elevated plasma catecholamine concentrations and enhanced synthesis and release of adrenaline from adrenal medulla