Levels of Amoxicillin and Ampicillin in Human Serum and Interstitial Fluid

Serum and subcutaneous chamber fluid (CF) dynamics of penicillin G, amnpicillin, and amoxicillin were studied in rabbits after single large parenteral doses comparable to doses used in treating gonorrhea and endocarditis. The effects of parenteral probenecid and ofinjection ofan antibiotic directly into a subcutaneous chamber ("intrachamber" injection) also were studied. Peak serum antibiotic concentrations exceeded peak CF concentrations and occurred sooner. Antimicrobial activity persisted longer in CF than in serum. Percent penetration [100 x (CF peak/serum peak)] of CF was least after intramuscular ampicillin and amoxicillin, was greatest after intrachamber ampicillin and intramuscular aqueous procaine penicillin G, and was related to duration of antibiotic concentration gradients from serum to CF. Intramuscular aqueous crystalline penicillin G resulted in higher serum and CF penicillin G concentrations than intramuscular aqueous procaine penicillin G, which prolonged the duration of penicillin G in serum and CF. Amoxicillin diffused into CF more readily than ampicillin. Probenecid resulted in higher early serum and CF antibiotic concentrations, but had little or no effect on duration of antibiotic activity. Intrachamber ampicillin resulted in more prolonged serum and CF ampicillin activity than intramuscular ampicillin, but much lower peak serum concentrations. The data suggest a possible means by which probenecid improves the efficacy of gonorrhea therapy with aqueous procaine penicillin G. Intrachamber administration of penicillins could be useful in treating experimental infections requiring prolonged therapy.

Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 42%

See 1 more Smart Citation

Serum and Subcutaneous Chamber Fluid Dynamics of Penicillins After Single Large Parenteral Doses

Tight

White

1980

“…The highest titer of cefotaxime in this group of patients was reached in the serum after 30 min and after 1 h in both the skin blister and the skin chamber fluids, but the concentrations of the were significantly lower (five to six times) than those found in the skin blister fluid (AUC, 51.72 ± 24.5) and in the serum (AUC, 48.48 ± 5.87). Two interpretations have been given to explain the different results shown above: the differences were due to the dilution of the exudate in the saline of the skin chambers of Tan et al (9), or the differences were due to the lower protein content in the skin chamber.…”

Section: Methodsmentioning

confidence: 96%

Suction skin blister, skin window, and skin chamber techniques to determine extravascular passage of cefotaxime in humans

Frongillo¹,

Galuppo²,

Moretti³

1981

We report the results obtained in a comparative study on the extravascular passage of cefotaxime, employing three different methods: suction skin blister, skin window, and skin chamber. Applying the skin blister method in two different ways, we also studied the influence that suction pressure and time lapse between blister formation and antibiotic injection had on the results obtained in order to standardize the method and establish repeatability of the results. Using the skin chamber method, we studied the influence that the different protein contents in the fluid used to fill the skin chamber had on extravascular concentrations.The study of interstitial extravascular passage of antibiotics in humans is an interesting problem which presents considerable limitations because of the lack of material available on dosage systems for the antibiotics. In fact, it is almost impossible to obtain sufficient quantities of the interstitial fluid to make such determining possible.Studies on the extravascular passage of antibiotics in humans have been made, using the skin window (7) and skin chamber methods (10) and more recently, the skin blister method (8).From the published results of studies on this subject, the great diversity of interstitial concentrations of the same antibiotic and the kinetic difference in relation to the methods being used are evident. We found, furthermore, that this difference may be related to diverse characteristics, mainly the different protein contents of the exudates obtained by different methods (R. F. Frongillo, Relazione XX Congresso Nazionale Societa Italiana Malattie Infettive e Parass., in press). It is, therefore, clear that none of the applied methods can produce liquids comparable to the interstitial fluid, since they are, for the most part, exudates or only apparent transudates.The first problem, therefore, is to establish a method which can be standardized easily and which by assuring reproducible results makes feasible a comparative study of the influence of various factors on the extravascular passage of the antibiotics.In recent in vivo and in vitro experiments, using the new cephalosporin cefotaxime, we studied the extravascular concentrations of this antibiotic and compared the results obtained by application of the skin window and skin chamber 22 methods with those obtained by using a suction skin blister method (6). MATERIALS AND METHODSSubjects. Patients 18 to 69 years of age (average age, 56), weighing 42 to 70 kg (average weight, 58 kg), were studied in the Infectious Diseases Institute of the University of Perugia, Italy.No clinical or biochemical alterations in kidney and liver functions were found on examining the patients, who had given their consent for the experiment.Cefotaxime. Cefotaxime (HR 756; Hoechst A. G., Frankfurt, Germany), in 1-g vials diluted in 1% lidocaine for intramuscular injection, was used. Blood and extravascular fluid samples were taken 30 min and 1, 2, and 4 h after the injection.Filter paper disks used in the skin window method were applied imm...

“…The diffusibility of the penicillins into ITF, using the skin window technique, appears to be related to the percentage of protein binding, as noted (7,9). Significantly poor diffufsibility was noted only with nafcillin and flucloxacillin, both ofwhich have approximately 10% or less of the free form in human serum (9).…”

Section: Resultsmentioning

confidence: 85%

Levels of Carbenicillin, Ticarcillin, Cephalothin, Cefazolin, Cefamandole, Gentamicin, Tobramycin, and Amikacin in Human Serum and Interstitial Fluid

Tan

Salstrom

1977

The ability of eight antibiotics (carbenicillin, ticarcillin, cefamandole, cephalothin, cefazolin, gentamicin, tobramycin, and amikacin) to enter human interstitial fluid was evaluated by the skin window technique. All of the antibiotics tested, except cefazolin, which has the highest percentage of protein binding, diffused into the interstitial fluid quite well. This study confirms our previous observation on the effect of high-percentage protein binding on diffusion of a drug into the minimally inflamed extravascular space.A method of measuring antibiotic levels in human interstitial fluid (ITF), using a skin window technique, has been described previously (9). Using this technique, we have determined the diffusibility of eight other antibiotics into human ITF.MATERIALS AND METHODS Volunteers. Written informed consent was obtained from male adult volunteers.Antibiotics. (i) Carbenicillin and ticarcillin. A double-crossover study was performed using these two drugs. Twelve volunteers were included in the study. Six volunteers were given 3 g of one drug over 30 min by intravenous infusion, and the remaining six were given 3 g of the other drug. The study was repeated after 1 week, and the volunteers received the drug that they had not received previously.(ii) Cephalothin, cefazolin, and cefamandole. Twelve volunteers participated in this study. Twelve received cefamandole, 10 received cephalothin, and 12 received cefazolin. Each volunteer was given a 1-g intravenous dose over a 30-min period.(iii) Amikacin, gentamicin, and tobramycin. A triple-crossover study was performed. Four volunteers were given 1.7 mg of gentamicin per kg, 1.7 mg of tobramycin per kg, or 7.5 mg of amikacin per kg. Each of the drugs was given intramuscularly. In parts 2 and 3 of the study, each volunteer was given whichever drug he had not previously received. Each part of the study was carried out at a 1-week interval.Serum samples. Venous blood was obtained before and at 1, 2, 3, and 4 h after antibiotic administration. The sera were separated after 45 min at 24°C and immediately frozen.ITF samples. The technique of obtaining ITF by using a skin window chamber has been described (9). These skin window fluid samples were removed completely, and the chambers were refilled with sterile isotonic saline at pH 6.0 within 5 min after the hourly venous blood samples were obtained.Assay of antibiotics. All of the antibiotics were assayed by using the agar well method of Bennett et al.(1). The test organism for ticarcillin and carbenicillin was Pseudomonas aeruginosa. Bacillus subtilis spore suspension (Difco Laboratories, Detroit, Mich.) was used as the test organism for the other antibiotics in the study.