Delivery of Antimicrobial Drugs Across Inflammatory Membrane in Rabbits

McCune, Robert M.

doi:10.1172/jci104105

Cited by 7 publications

(3 citation statements)

References 12 publications

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“…The results of our experiments in which single intramuscular injections of the antibacterial were administered to dogs are in good agreement with those of Chisholm et al (1968) and Verwey & Williams (1962a, b) and indicate that penicillins, even those which are highly bound to plasma proteins, penetrate well into extravascular spaces. This observation is supported by other workers (Abraham, Chain, Fletcher, Florey, Gardner, Heatley & Jennings, 1941;Brown, 1964;Florey, Turton & Duthie, 1946;Jawetz, 1946;McCune, 1960;Nathanson & Liebhold, 1946;Ungar, 1950;Weinstein, Daikos & Perrin, 1951;Werner, Knight, McDermott, Adams & Dubois, 1954;White, Lee & Alverson, 1946). Our experiments therefore indicate that penicillins penetrate readily from plasma to extravascular fluids as represented by peripheral lymph, thereby achieving good antibacterial concentrations of the free active penicillins in the tissues.…”

Section: Discussionsupporting

confidence: 89%

The distribution of antibacterial agents between plasma and lymph in the dog

Acred¹,

Brown²,

Clark³

et al. 1970

British J Pharmacology

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Summary1. Plasma, peripheral and thoracic lymph concentrations of penicillin V, phenethicillin, carbenicillin, ampicillin, cloxacillin, penicillin G, chloramphenicol and sulphadiazine were determined at various time intervals up to 6 h following intramuscular administration of 50 mg/kg to dogs. 2. Peak plasma concentrations of the penicillins occurred within half an hour after administration with the peak lymphatic concentrations occurring 15 to 3 h afterwards. For the remaining period of the test the concentration in the lymph exceeded the corresponding concentra-tion in the plasma. Sulphadiazine gave concentrations in thoracic lymph equal to the plasma concentration, but the peripheral lymph concentrations were lower while the concentrations of chloramphenicol in both peripheral and thoracic lymph were always lower than the plasma concentrations. 3. After the peak concentrations were reached, the concentration curves for penicillins in lymph followed the same pattern as found in plasma, the penicillin concentrations declining exponentially. Sulphadiazine produced more persistent levels both in lymph and in plasma while the concentrations of chloramphenicol were still rising 6 h after administration. 4. The free concentrations of penicillin in lymph were equal to the free concentrations in plasma, whereas the concentrations of free sulphadiazine and chloramphenicol in lymph were less than those in the plasma.

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Section: Discussionsupporting

confidence: 89%

The distribution of antibacterial agents between plasma and lymph in the dog

Acred¹,

Brown²,

Clark³

et al. 1970

British J Pharmacology

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“…Pts had follow-up evaluations of testosterone (T) levels, thymic measurements on CT scan and assessments of naïve T-cells. Thymic evaluations were based on a previously established radiographic measure, the thymic index [ 2 ]. Changes in naïve CD 4 T-cells, defined as CD45RA+CD31+, and T-cell receptor excision circles (TRECs) were also evaluated.…”

Section: Methodsmentioning

confidence: 99%

Impact of androgen deprivation therapy on the thymus and the production of naïve T-cells

Madan

Frances²,

Jochéms

et al. 2013

j. immunotherapy cancer

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“…The area under the curve of gentamicin concentration in serum was 1.47 times that of pleural effusion and 1.29 times that of empyema. Prolonged persistence of antibiotics in inflammatory exudates was previously described for several antibacterial agents (1, 8,24). It is possible that in our model the leukocytes in the pleural cavity bound the' aminoglycoside and thus prolonged its half-life (3).…”

Section: Discussionmentioning

confidence: 67%

Pharmacokinetics and therapeutic efficacy of gentamicin in an experimental pleural empyema rabbit model

Shohet

Yellin

Meyerovitch

et al. 1987

Antimicrob Agents Chemother

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The pharmacokinetics and therapeutic efficacy of gentamicin were investigated in an experimental pleural empyema rabbit model. Pleural effusion was induced by the intrapleural administration of turpentine, and empyema was induced by direct inoculation of the effusion with Kkebsiella pneumoniae. Pleural empyema compared with effusion was characterized by lower pH, oxygen tension (PaO2), and glucose levels and higher leukocyte count, lactic acid concentration, and PaCO2. After a single administration, gentamicin was first detectable in the pleural fluid at 60 min, whereas peak levels in empyema were observed at 180 min. Gentamicin persisted in the empyema longer than in blood. Animals treated with gentamicin only had 60% bacterial cure on day 7; those treated with gentamicin in an oxygen chamber had 100% cure on day 5 (P = 0.004). Low oxygen tension diminished the antibacterial efficacy of gentamicin in this model. An increase in oxygen tension improved the therapeutic results without alterationi of the pharmacokinetics of gentamicin.Pleural empyema poses a serious medical problem with a high rate of complications. Although the optimal treatment of pleural empyema has not been well defined, it is usually prolonged and often requires drainage. Staphylococcus aureus, Streptococcus pneumoniae, and anaerobic bacteria are the organisms most frequently isolated from empyema after pneumonia, whereas aerobic gram-negative enteric bacilli are the most predominant pathogens in postoperative patients (4,20,22,23).Defective bacterial opsonization, absence or decrease in intact complement, and decreased leukocyte functions may all contribute to the low rate of spontaneous cure of pleural empyema (7,21). Insufficient antibiotic penetration and other unfavorable local conditions may further hamper the success of antibiotic therapy, necessitating surgical intervention (10).In this investigation, we evaluated the pH, oxygen tension (PaO2), PaCO02, glucose, lactic acid concentrations, and leukocyte count of experimental empyema fluid in rabbits. The therapeutic effect of gentamicin alone and gentamicin together with oxygen was investigated as well.MATERIALS AND METHODS Fifteen male and female New Zealand White rabbits weighing 2 to 3 kg were anesthetized with ketamine (Ketalar; Parke, Davis & Co.) and xylazine (Rompun; Bayer AG), their chest fur was clipped, and the underlying skin was scrubbed with iodine. A 16-gauge Venflon cannula capped with a rubber stopper to prevent air entry was introduced into the, right pleural space through a longitudinal paravertebral skin incision performed between ribs 8 and 9 in a method described by Sahn and Potts (16). The cannula was placed by being pointed caudally. After insertion of the cannula, the cap was removed for a few seconds, allowing air to be sucked into the pleural space and thus creating a pneumothorax, which was evacuated immediately by suction. The cannula was then secured to the subcutaneous tissue, and the overlying skin was closed with Dexon sutures. Pleural effusion was induce...

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Delivery of Antimicrobial Drugs Across Inflammatory Membrane in Rabbits

Cited by 7 publications

References 12 publications

The distribution of antibacterial agents between plasma and lymph in the dog

The distribution of antibacterial agents between plasma and lymph in the dog

Impact of androgen deprivation therapy on the thymus and the production of naïve T-cells

Pharmacokinetics and therapeutic efficacy of gentamicin in an experimental pleural empyema rabbit model

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