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Biomedical subjects

M Barza

Publications and source records attributed to M Barza.

At least 163 records · Page 9Linked to original sources

The effect of corticosteroids in the treatment of experimental bacterial endophthalmitis.

We evaluated the effects of the addition of corticosteroids to antibiotic therapy in the treatment of staphylococcal endophthalmitis in rabbits. Twenty-four hours after the induction of infection with Staphylococcus aureus, penicillin G, penicillin G and dexamethasone or prednisolone, or saline was injected retrobulbarly for ten days. Afterward, there was no ophthalmoscopic difference between the penicillin and corticosteroid-treated group and those animals receiving only penicillin G. At day 60, however, the fundus was visible in 64% of eyes treated with penicillin G with corticosteroids in contrast to 39% of those eyes treated only with penicillin G (P less than .025). The results between dexamethasone and prednisolone use were not significant. Retrobulbar corticosteroids in combination with effective antibiotic therapy effectively treated experimental bacterial endophthalmitis.

Animals↗

Pharmacokinetics of lincomycin and clindamycin phosphate in a canine model.

Linomycin and clindamycin phosphate were studed in a canine model in which acute biliary obstruction was produced during iv infusion of antibiotic. Hepatic and renal extraction, bilary and renal excretion, and concentrations in liver and kidney were measured. Total and nonesterified clindamycin were assayed. The antibiotics were taken up by the liver at similar rates; however; the rates of excretion and concentration in bile were significantly higher for lincomycin than for clindamycin. Biliary obstruction did not affect the concentration of either antibiotic in canalicular bile. Lincomycin was extracted by the kidneys and excreted into urine at a much higher rate than was clindamycin. Concentrations of nonesterified clindamycin in the hepatic vein were higher than those in the portal vein, an observation suggesting metabolic activation within the liver. This relation was reversed by bilary obstructon. The results in this canine model indicate a greater role for the kedney in the disposition of lincomycin than in that of clindamycin, major differences between the rates of biliary excretion of the two agents, and a probable change in the metabolism of clindamycin procued by acute bilary obstruction.

Animals↗

Extraction of antibiotics from the circulation by liver and kidney: effect of probenecid.

An experimental canine model was designed to measure directly the uptake, storage, and excretion of antibiotics by the liver and kidney. At equilibirum the rate of uptake of penicillin G, cephalothin, and nafcillin by these organs was about 80% of the rate of intravenous infusion of each antibiotic. Penicillin G and cephalothin were extracted mainly by the kidneys, and nafcillin by the liver. Injection of probenecid virtually abolished the difference in concentration of antibiotic between afferent and efferent vessels of the liver and kidney after 30-45 min. Renal tubular secretion of penicillin G and cephalothin was suppressed, and their levels in renal tissue were increased. These findings militate against any primary limitation by probenecid of access of antibiotic to the renal parenchyma. A marked sustained increase (60%-70%) in the rate of portal flow followed injection of probenecid, and the concomitant percentage of nafcillin extracted by the liver declined significantly. Because of the circulatory changes, a specific effect of probenecid on acess of nafcillin to the liver could not be proved.

Animals↗

Predictability of blood levels of gentamicin in man.

Data from 42 patients were analyzed to determine the predictability of the peak serum level and the t1/2 of gentamicin on the bases of age, sex, body weight, serum concentration of creatinine, and blood hematocrit. Renal function was normal in 21 patients and impaired in 21. The most striking finding was the relatively poor predictability of t1/2 of gentamicin from serum concentration of creatinine. The overall correlation coefficient was 0.749 (P less than 0.001) in contrast to values of greater than 0.9 reported by others. tthere was a significant correlation of the t1/2 of gentamicin with the reciprocal of hematocrit (r * 0.647, P less than 0.001). Linear regression equations taking account of sex, serum creatinine concentration, and reciprocal of hematocrit provided a somewhat higher correlation coefficient (0.821) with the t1/2 of gentamicin than did the equation including serum creatinine concentration alone but were still not fully satisfactory. Thus the pharmacokinetics of gentamicin may not be adequately predictable from standardized equations or nomograms.

Adolescent↗

Renal tubular transport of penicillin G and carbenicillin in the rat.

The pattern of transport of penicillin G and carbenicillin was examined directly in the rat kidney by means of micropuncture studies. Samples of plasma, tubular fluid, and urine were assayed for antibiotic content by an agar diffusion technique. Secretion accounted for 67% of the penicillin G but for only 37% of the carbenicillin present in the proximal tubule. No further net secretion of either agent could be detected in the distal nephron. Net secretion of penicillin G decreased from 67% in the distal tubule to 60% in the urine (P less than 0.05%); this reduction correlated with reabsorption of water from the collecting ducts. Both penicillin G and carbenicillin were secreted by the proximal tubule of the rat nephron, but the latter was secreted at a lower rate than the former. A significant fraction of penicillin G was reabsorbed from the collecting ducts under conditions of maximal antidiuresis.

Animals↗

Effect of diuretics on urinary excretion of cephalothin in humans.

Diuretics and antibiotics are frequently used concomitantly. The possibility of drug interactions led us to study the effects of several diuretics on the renal elimination of cephalothin. Five healthy volunteers received a constant infusion of 500 mg of sodium cephalothin per h for 9 h on 4 consecutive days. Each day, after the third hour of infusion, the subjects were given one of the following in varying order: (i) furosemide (1 mg/kg, intravenous), (ii) mercaptomerin (250 mg, intramuscular), (iii) mannitol (25 g, intravenous), or (iv) no diuretic (control day). Fluid losses were replaced hourly. Serum and complete urine collections were obtained each hour and assayed for creatinine and cephalothin (bioassay). Clearances (milliliter per minute) and urinary excretions (milligram per hour) of cephalothin did not differ either when the diuretic day values were compared with control day, or when pre- and postdiuretic results on the same day were compared. Creatinine clearances were not affected by diuretics except for a transient rise after furosemide.

Adult↗

Relation between lipophilicity and pharmacological behavior of minocycline, doxycycline, tetracycline, and oxytetracycline in dogs.

Four tetracyclines were studied in dogs to determine the relation between their lipophilicity and various other pharmacological characteristics. Lipid solubility correlated inversely with the mean concentration of drug in arterial plasma and renal uptake and excretion, and directly with the biliary concentration gradient (level in bile/level of free drug in serum). Only the more lipophilic congeners minocycline and doxycycline passed the blood-brain and blood-ocular barriers in detectable concentrations. Mean levels of minocycline in the brain exceeded those of doxycycline by almost threefold; the difference was of borderline statistical significance (P = 0.05 to 0.1). Lipophilicity correlated inversely with the concentration of antibiotic in renal medulla but not in renal cortex or in the liver. When intestinal loops containing saline, milk, or 10% Gelusil were studied, the only combination exhibiting striking intraluminal accumulation was doxycycline in milk. These results indicate that lipophilicity correlates with many, but not all, of the transport characteristics of tetracycline antibiotics.

Animals↗