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Biomedical subjects

A Meulemans

Publications and source records attributed to A Meulemans.

At least 73 records · Page 4Linked to original sources

Permeability of nitroimidazoles in rat cortex.

The right cerebral hemisphere of the rat was perfused in situ by retrograde bolus infusion of some nitroimidazole drugs into the external carotid artery. The right jugular vein served to collect blood samples. Drugs were continuously measured in the right cortex by microvoltametric electrodes and in blood samples by high-performance liquid chromatography during a few minutes. Cerebrovascular permeability coefficients of six nitroimidazoles ranged from 0.8 X 10(-4) to 3 X 10(-6) cm X s-1 and were directly proportional to the octanol-water partition coefficient of the solute. Thus, microvoltametry is a new method to study cerebrovascular transfer in the rat of electroactive antibiotics.

Animals↗

Penetration of imipenem and cilastatin into cerebrospinal fluid of patients with bacterial meningitis.

The penetration of imipenem and cilastatin into the cerebrospinal fluid (CSF) was determined in patients with bacterial meningitis. Four 1000 mg doses [corrected] of both imipenem and cilastatin were infused intravenously over 20-30 min at 6 h intervals, first between days 2 and 4, and again, whenever possible, between days 11 to 20, in 12 patients with bacterial meningitis undergoing treatment with other antibiotics. Concentrations of imipenem and cilastatin in serum and cerebrospinal fluid samples obtained either at 60, 90 or 120 min following the fourth dose were measured by high pressure liquid chromatography. Concentrations of imipenem in CSF ranged from 0.5 to 11 mg/1 and concentrations of cilastatin ranged from 1.1 to 10.5 mg/1, depending on the sampling time and the time elapsed since the onset of the disease.

Adult↗

Kinetics of gentamicin in plasma of nonpregnant, pregnant, and fetal guinea pigs and its distribution in fetal tissues.

Nonpregnant and pregnant guinea pigs in the last third of gestation were injected intramuscularly with 4 mg of gentamicin per kg, and drug concentrations in plasma were determined by radioimmunoassay at several intervals after injection. The maximum gentamicin concentration was lower in pregnant than in nonpregnant animals (14.6 +/- 0.7 micrograms/ml versus 21.6 +/- 0.7 micrograms/ml), and the peak time occurred significantly later (0.57 +/- 0.12 h versus 0.13 +/- 0.02 h). Four hours after gentamicin injection, drug concentrations in plasma were 2.1 +/- 0.8 and 0.3 +/- 0.1 micrograms/ml in pregnant and nonpregnant animals, respectively. Pregnant animals therefore eliminated the drug from their plasma more slowly. These data provide good evidence that the kinetics of plasma gentamicin varies in pregnant females because its volume of distribution was larger in pregnant than in nonpregnant animals. Detectable but small amounts of gentamicin (less than or equal to 0.50 microgram/ml) were found in the plasma of 46 of 57 fetuses. However, no net variations in these concentrations were observed during the period between 15 min and 6 h after injection to the mother. Gentamicin concentrations were also determined in the kidneys, liver, lungs, heart, and brain of fetal guinea pigs after administration to their mothers of one daily injection of 4 mg/kg for 7 days. Gentamicin was present in all these fetal organs; however, as in the adult organs, the kidneys contained far more than any of the others. Gentamicin concentrations were not significantly different in the kidney cortex and medulla (1.79 +/- 0.16 versus 1.48 +/- 0.92 micrograms/g), indicating that, contrary to what is observed for adults, renal accumulation of gentamicin in the fetus does not occur preferentially in the cortex.

Animals↗

[Aztreonam. Diffusion into bronchial mucus].

In a prospective study of antibiotics' diffusion into human bronchial mucus, we compared serum and mucus concentrations of aztreonam, a new beta lactam belonging to the monobactam group. Twenty patients were given aztreonam (1 g twice a day) for an acute purulent exacerbation of chronic bronchitis and divided into four groups according to the time of sampling (0.5, 1, 1.5 or 3 h). Samples were taken on the first and third treatment days. Antibiotic concentrations were assayed using agar diffusion and HPLC. Aztreonam concentrations were low, similar to those achieved with other beta lactams. According to the time sampling, levels ranged from 0.27 to 1 mg/l and 0.4 to 1.15 mg/l on the first and third treatment days respectively. Corresponding serum levels were 90 mg/l and 30 mg/l, respectively 30 mn and 3 h after dose ingestion.

Aztreonam↗

[Penetration of piperacillin into the cerebrospinal fluid of patients with purulent meningitis].

Ten patients with purulent meningitis received 3 intravenous injections of 4 g piperacillin at intervals of 8 hours, in addition to the usual antimicrobial treatment. Piperacillin was assayed in serum and CSF by high performance liquid chromatography. The mean CSF concentration of the drug was 9.2 micrograms/ml and its mean percentage of penetration was 22,7%. There were no significant differences in CSF concentrations between days 2 to 4 (inflamed meninges) and days 10 to 20 (patient cured). It is concluded that piperacillin shows good CSF penetration and could be useful to treat selected cases of meningitis due to Gram-negative bacilli.

Adolescent↗

On-line pharmacokinetics of chloramphenicol in rat cortex by in vivo electrochemical detection.

In vivo electrochemical detection of chloramphenicol in rat cortex was investigated with microelectrodes after intravenous injection of chloramphenicol succinate (170 mg X kg-1). A classical pharmacokinetic study with high-performance liquid chromatography (HPLC) determination of chloramphenicol was performed. The two methods gave the same result when chloramphenicol and chloramphenicol succinate were added for the HPLC assay and compared with the voltametric assay. Clinical applications of this new method are suggested.

Animals↗

Albendazole as a potential treatment for human hydatidosis.

The pharmacokinetics of albendazole was evaluated in 11 patients with hydatid disease who underwent surgery 12 h after the last dose of drug. Albendazole and its main metabolite, albendazole-sulphoxide, were assayed in the serum from peripheral and portal blood, the liver, bile, lungs, and hydatid cyst walls and fluid. After a 10-14 mg/kg daily oral dose of albendazole, concentrations of 1844 +/- 904 ng/g wet tissue of albendazole-sulphoxide were found in the liver and 749 +/- 34 ng/g wet tissue in the lungs. The level in hydatid cyst fluid was 921 +/- 314 ng/ml. The drug was also excreted through the bile. The same daily oral dose produced very stable blood levels after 2 to 4 days of treatment (600-1000 ng/ml). In another part of the study 3 patients with liver cysts, 2 with peritoneal cysts, and 5 with bone cysts received 7 mg/kg twice a day prophylactically and/or therapeutically for 30 days. In all cases the treatment was repeated several times after intervals of 2 weeks. The 3 patients with liver cysts were cured (probably due to treatment); there was no recurrence in the 2 patients with peritoneal cysts and very slight improvement in the 5 cases with bone cysts. The drug was clinically and biologically extremely well tolerated.

Administration, Oral↗

[Treatment of enterobacterial meningitis in adults with intravenous lamoxactam].

Meningitis caused by Gram-negative bacilli creates difficult problems since most strains are multiresistant. The purpose of this study was to evaluate the effectiveness of lamoxactam administered intravenously. Eleven patients admitted to an intensive care unit with meningitis due to Gram-negative bacilli were treated with this antibiotic, administered alone in 9 cases. Three patients had ventriculitis. Eight survived. The MICs ranged from 0.06 to 0.5 microgram/ml in 10 cases. The CSF was sterilized and rapidly became normal. Meningeal concentrations varied from 1-5 to 62 micrograms/ml and the CSF was bactericidal. In one female patient the CSF was sterile on the 5th day of treatment but remained abnormal; the meningeal concentration of lamoxactam (35 micrograms/ml) was much higher than the MIC (2 micrograms/ml) but below the MBC (128 micrograms/ml), which was consistent with the absence of bactericidal effect of the CSF. Owing to its very low CMIs and satisfactory passage through the blood-brain barrier, lamoxactam administered alone can be successful in the treatment of Gram-negative meningitis and ventriculitis. However, the bactericidal effect of the CSF should be rapidly assessed.

Adult↗

[Treatment of 18 cases of purulent meningitis with moxalactam. Pharmacokinetic data].

The diffusion of moxalactam into cerebrospinal fluid was studied in 18 hospital patients with purulent meningitis treated with this antibiotic. Moxalactam was administered by intravenous infusion in doses of 2 g 8-hourly (6 g/24 h). Treatment lasted from 10 to 30 days depending on the pathogen involved. The antibiotic was assayed by high performance liquid chromatography simultaneously in serum and CSF at the time of lumbar puncture. Depending on the time elapsed since the end of the infusion, the mean CSF concentrations ranged from 32.8 to 9.37 micrograms/ml at the beginning of the disease and from 23.75 to 3.78 micrograms/ml toward the end of treatment. These values were notably higher than the MIC for most of the micro-organisms encountered. All patients were cured.

Adult↗

Ethacrynic acid facilitates gentamicin entry into endolymph of the rat.

Influence of ethacrynic acid (EA) upon gentamicin kinetics in perilymph and endolymph was studied in rats that were given a constant-infusion of gentamicin (150 micrograms/min) and EA (140 micrograms/min). Inner ear fluids and plasma were sampled up to 5 h. The purity of the endolymph was ensured by measurement of sodium and potassium concentrations. Gentamicin assay was done with a modified radioimmunoassay. Results show that EA facilitates the entry of gentamicin into endolymph, while it does not affect the kinetics of the drug in perilymph. Although the mechanism of this facilitation remains unclear, this result may account for the ototoxic potentiation reported between EA and aminoglycoside antibiotics.

Animals↗

Gentamicin persistence in rat endolymph and perilymph after a two-day constant infusion.

The kinetics of gentamicin in the inner ear fluids of rats were studied up to 15 days after cessation of a 2-day constant infusion of 10 micrograms/min. In endolymph, the concentration of gentamicin persisted at about 1 microgram/ml for up to 15 days, precluding the determination of the half-life of the drug in this fluid. In perilymph, gentamicin cleared more slowly than after a shorter period of infusion. These results suggest that the tissues of the inner ear could bind the aminoglycoside and then slowly release it into the surrounding fluids.

Animals↗

Penetration of ceftazidime into cerebrospinal fluid of patients with bacterial meningitis.

Four 2-g doses of ceftazidime were infused intravenously over 30 min at 8-h intervals, first between days 2 and 4 and again between days 11 and 20, in 11 patients with bacterial meningitis undergoing treatment with other antibiotics. Concentrations of ceftazidime in serum and cerebrospinal fluid samples obtained 120 or 180 min after dose 4 were measured by high-pressure liquid chromatography. Concentrations in cerebrospinal fluid ranged from 2 to 30 micrograms/ml, depending on the sampling time and the time elapsed since the onset of the disease.

Adolescent↗

[Not Available].

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Belgium↗

Moxalactam penetration into cerebrospinal fluid in patients with bacterial meningitis.

Penetration of moxalactam into the cerebrospinal fluid was studied in 11 patients with bacterial meningitis undergoing treatment with other antibiotics. Moxalactam at a dose of 20 mg/kg was administered as three 30- to 45- min infusions at 8-h intervals, once between days 2 and 4 and a second time between days 11 and 20 of treatment with the other antibiotics. Serum and cerebrospinal fluid were sampled 60, 90, or 120 min after the third moxalactam dose for measurement of the concentration of this drug by high-performance liquid chromatography. The concentration of moxalactam in cerebrospinal fluid ranged from 1.5 to 11 micrograms/ml, depending on the sampling time and the time elapsed since the onset of the disease. These concentrations in cerebrospinal fluid were equal to or higher than the minimum inhibitor concentrations for Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae (including ampicillin-resistant strains), and most of the gram-negative bacilli except for Pseudomonas aeruginosa. These results show that moxalactam has good penetrability when the meninges are inflamed and that it might be considered in cases of bacterial meningitis when the susceptibility of the pathogen indicates its usefulness.

Adult↗

[Pharmacokinetic study of flubendazole in human hydatid disease caused by Echinococcus granulosus. Preliminary results (author's transl)].

A pharmacokinetic study of flubendazole was carried out, using a radioimmunological method, in patients with hydatid disease about to undergo surgery; there was no evidence of drug penetration into the walls or contents of the cysts. Another study, carried out simultaneously in subjects without hydatid disease, showed very high concentrations of the drug in liver tissue and in bile. These results should not be taken as arguments against the effectiveness of flubendazole, but should encourage the setting up of further randomized pharmacokinetic studies.

Adult↗