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The penetration of several antibiotics into human polymorphonuclear leucocytes was measured with a bioassay. The aminoglycosides (gentamicin, netilmicin), oxacillin and LY146032, a new lipopeptidic antibiotic, had a penetration which was generally less than 60%, whereas new fluoro-quinolones (enoxacin, ciprofloxacin, CI934, Ro236240) and rifamycins (rifampicin, LM427) were concentrated 2.4 to 14.2-fold. The concentration of vancomycin and teicoplanin associated with the neutrophils appeared to be saturable over the range of extracellular concentrations tested (5-20 mg/l). Coumermycin, an inhibitor of DNA-gyrase, was highly concentrated (11.3 to 16.6-fold) within the neutrophils. The penetration of clindamycin and erythromycin was low (0.60- to 1.48-fold).

We have studied amphotericin B concentrations in tissues of 13 cancer patients who died after having received 75 to 1,110 mg (total dose) of amphotericin B-deoxycholate for suspected or proven disseminated fungal infection. Amphotericin B concentrations were measured by high-pressure liquid chromatography (HPLC) and by bioassay, the latter being done on tissue homogenates as well as on tissue methanolic extracts. The fungistatic and fungicidal titers of the tissue homogenates were also tested against three strains of Candida albicans and one strain of Aspergillusfumigatus. Tissue concentrations of amphotericin B measured by HPLC varied with the tested tissues as well as with the total dose of amphotericin B-deoxycholate administered and ranged from 0.4 to 147.1 ,ug/g. A mean of 38.3% (range, 23.0 to 51.3%) of the total dose was recovered by HPLC from all of the tested organs. Bioassay of tissue methanolic extracts reached 58 to 81% of the concentration measured by HPLC, whereas only 15 to 41% was recovered from the homogenates. Overall, 27.5% of the total dose was recovered from the liver, 5.2% was recovered from the spleen, 3.2% was recovered from the lungs, and 1.5% was recovered from the kidneys. The median concentration in bile was 7.3 ,ug/ml, suggesting that biliary excretion could contribute to amphotericin B elimination to an estimated range of 0.8 to 14.6% of the daily dose. Fungicidal titers were seldom measured in tissues, but fungistatic titers were observed and were linearly correlated with amphotericin B concentration measured by HPLC. In conclusion, only a small proportion of the amphotericin B administered as amphotericin B-deoxycholate to patients seems diffusible and bioactive.Amphotericin B remains the therapy of choice for invasive fungal infections in immunocompromised patients (2, 8), but treatment failures are still numerous, especially in patients with severe and persisting neutropenia (9,16). Despite the widespread use of amphotericin B during the last 30 years, the pharmacokihetic profile of this agent in humans remains unclear. Concentrations of amphotericin B in serum measured after the administration of conventional doses (0.4 to 1 mg/kg per day) range from 0.5 to 2 ,ug/ml and usually exceed