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Biomedical subjects

G Benoni

Publications and source records attributed to G Benoni.

At least 73 records · Page 4Linked to original sources
PubMed1988

Pharmacokinetics and human tissue penetration of flurithromycin.

The relationship between concentrations in serum and levels in tissue of flurithromycin, a new fluorinated macrolide, was determined in patients undergoing maxillofacial surgery and thoracotomy. All patients received 500 mg of flurithromycin orally every 8 h. Drug levels in serum, bone, soft tissue, lung, and pericardial fluid were determined microbiologically. The total amount of antibiotic per gram of tissue was calculated on the basis of the concentration in the supernatant of the homogenate. From the parallel course between free concentrations in serum and calculated contents in interstitial fluid tissue, it was concluded that the tissues examined were easily accessible by flurithromycin; penetration values measured by the ratio of areas under the curve were 8.3 for lung, 3.6 for bone, and 0.8 for soft tissue. The results of the pharmacokinetic study suggest that accumulation of the drug during repetitive multiple doses is predictable. Mean residence times were 10.2 and 8.3 h in groups 1 and 2, respectively. For bacteriostatic drugs such as macrolides, not only very high but also prolonged concentrations in tissue lead to favorable therapeutic result.

Adult↗
PubMed1987

Multisystem toxicity of indomethacin: effects on kidney, liver and intestine in the rat.

Some studies on the relationships among toxic effects in rat liver, kidney and intestine have been carried out. Indomethacin caused a marked reduction in microsomal enzymes, such as cytochrome P450, cytochrome b5 and aminopyrine N-demethylase in the kidney and the liver, greater in the former and for a shorter time than in the latter. Indomethacin induced intestinal lesions and marked overgrowth of intestinal bacteria, mainly of aerobic bacteria in the first 24 hours after its administration and anaerobic bacteria such as Clostridii in the second day. These findings enable us to suggest that the drug induces multisystem lesions through different mechanisms involving either a direct effect on the tissue or other microbiological or pharmacological factors.

Aminopyrine N-Demethylase↗
PubMed1987

Imipenem kinetics in serum, lung tissue and pericardial fluid in patients undergoing thoracotomy.

Imipenem serum pharmacokinetics, lung tissue and pericardial fluid concentrations were measured in 10 patients undergoing thoracotomy, following a 1 g intravenous infusion of imipenem-cilastatin. The serum concentrations of imipenem 0.5 h and 4 h after the end of the 40 min infusion were 53.3 (+/- 16.7) and 2.0 (+/- 0.3) mg/l, respectively. The concentration of imipenem in lung tissue at 1 h was lower than in pericardial fluid and at 2.25 h the mean concentration of imipenem in pericardial fluid was 10.5 mg/l, vs. 0.28 mg/kg of lung tissue. Imipenem concentrations in pericardial fluid remained above 5 mg/l, well above the MIC for most pathogens, for 1 h whereas in pericardial fluid the concentration was 10.5 mg/l at 2.25 h.

Body Fluids↗
PubMed1987

Two-cycle cisplatin kinetics in patients with ovarian and mammary cancer.

The kinetics of platinum (Pt) in patients treated for two-cycle therapy with cis-DDP for ovarian or mammary carcinoma were investigated. Cis-DDP, at a dose of 65 mg/m2, was administered i.v. over 60 min to 6 patients every 3 weeks. Plasma was collected before and 1, 2, 4, 8, 24, and 48 h after the start of the first and second infusions. The levels of Pt in the patients' plasma were determined by flameless atomic absorption spectroscopy. Plasma levels were analyzed by a two-compartment open pharmacokinetic model. Plasma decline was biphasic, both after the first and the second cycle. In all patients, the calculated t1/2 of the rapid phase increased after the second cycle (from a mean value of 0.39 h to 2.45 h), whereas the t1/2 of the slow phase increased about threefold in 3 subjects. In the latter, we observed an increase of AUC and a decrease of total body clearance.

Adult↗
PubMed1987

Kinetics of platinum in cancer patients treated with cisplatin at different doses.

In previous work the authors observed that platinum (free and bound) does not seem to accumulate in the peripheral compartment following the administration of two courses of cisplatin (cis-DDP) therapy (65 mg/m2) in patients with mammary and ovarian cancer. The aim of the present work was to study the disposition of platinum (Pt) after a higher dose of cis-DDP, to verify the rate of free drug penetration into the tissue and to observe changes in protein binding relative to the dose. cis-DDP, at the dose of 100 mg/m2, was administered i.v. over 60 min to patients with lung cancer. Serum and urine were collected before infusion and at various intervals afterwards. The plasma and urine levels of Pt were determined by flameless atomic absorption spectrophotometry, using a Varian model AAS 1475-GTA 95. Serum levels were analysed by a two-compartment open pharmacokinetic model. After the higher dose there was a substantial increase in central volume Pt and slight increase in peripheral volume Pt as compared with levels observed previously at the lower dose. In some subjects receiving high doses elimination half-life decreased and total body clearance increased, while in others these kinetic parameters were unchanged in comparison with those observed after a low dose. Protein binding seems to influence the persistence of platinum in the vascular space, modifying to a minor degree tissue penetration of the drug.

Adult↗
PubMed1986

Oxygen free radicals interact with indomethacin to cause gastrointestinal injury.

In the present study it was shown that, unlikely MK447, a known oxygen free radical compound, PGE2 is much less effective against indomethacin-induced G.I. ulcers than against ethanol damage. It seems likely that factors other than PG deficiency (such as oxygen free radicals), could be involved in the pathogenesis of NSAID-induced G.I. damage. Some compounds that can capture free radicals (aminopyrine, thiourea and its derivative, MK 447) or that inhibit the lipoxygenase pathway (MK 447, salicylazosulfapyridine, BW 755, benoxaprofen) are able to abolish indomethacin-induced G.I. damage. After irradiation with hydroxyl free radicals, indomethacin reacts with them to cause marked G.I. injury, even at a submaximal dose, one poorly ulcerogenic by itself. The above findings suggest that oxygen free radicals are one of the causal factors in the formation of NSAID-induced G.I. side effects. Some of the data in this paper were presented at Fermo, August 31, 1984 (Advanced course on 'oxygen and sulfur radicals in chemistry and medicine') and at the 9th Iuphar International Congress of Pharmacology in London, July 30, 1984.

Animals↗
PubMed1986

Penetration of ceftriaxone into human pleural fluid.

The pharmacokinetics of ceftriaxone were studied for seven patients with pleural effusion of various etiologies. All patients received 1 g of antibiotic, administered as an intravenous bolus. The pleural fluid had a high total protein content (6.0 g/dl). Ceftriaxone levels in plasma and in pleural fluid were determined by the agar well diffusion technique. Total and free drug concentrations in pleural fluid reached 7 to 8.7 and 3.8 to 2.3 micrograms/ml, respectively, in 4 to 6 h. The disappearance of the drug from the pleural fluid was very slow. In these patients, therapeutic ceftriaxone levels were present for at least 53 h in pleural fluid.

Adult↗
PubMed1984

Penetration of ceftazidime in human pericardial fluid and lung tissue.

The penetration of ceftazidime in pericardial fluid and lung tissue was investigated in 14 thoracotomized patients, who had normal renal function and did not receive any antibiotic treatment before thoracotomy. The drug (28 mg/kg) was given by i.v. Blood, pericardial fluid and lung tissue samples were taken over the next 5 hours. Concentrations of ceftazidime in the lung tissue were very high in the first hour and over the 200 and 300 min time interval, the ratio between serum and lung tissue levels was 0.7. The correlation coefficient between pericardial fluid, serum ratio and time was calculated to be of 0.99 (P less than 0.001). From these data we can observe that ceftazidime rapidly diffuses into the pericardial space and lung tissue where good concentrations (5.4 mcg/g) persist for at least 5 hours.

Adult↗