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Exogenous pulmonary surfactant as a drug delivering agent: influence of antibiotics on surfactant activity
Author(s) -
Veen Annemarie,
Gommers Diederik,
Mouton Johan W.,
Kluytmans Jan A.J.W.,
Krijt Erik Jan,
Lachmann Burkhard
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15442.x
Subject(s) - pulmonary surfactant , tobramycin , chemistry , in vivo , ceftazidime , pharmacology , saline , chromatography , antibiotics , medicine , anesthesia , biochemistry , biology , gentamicin , bacteria , genetics , microbiology and biotechnology , pseudomonas aeruginosa
1 It has been proposed to use exogenous pulmonary surfactant as a drug delivery system for antibiotics to the alveolar compartment of the lung. Little, however, is known about interactions between pulmonary surfactant and antimicrobial agents. This study investigated the activity of a bovine pulmonary surfactant after mixture with amphotericin B, amoxicillin, ceftazidime, pentamidine or tobramycin. 2 Surfactant (1 mg ml −1 in vitro and 40 mg ml −1 in vivo ) was mixed with 0.375 mg ml −1 amphotericin B, 50 mg ml −1 amoxicillin, 37.5 mg ml −1 ceftazidime, 1 mg ml −1 pentamidine and 2.5 mg ml −1 tobramycin. Minimal surface tension of 50 μl of the mixtures was measured in vitro by use of the Wilhelmy balance. In vivo surfactant activity was evaluated by its capacity to restore gas exchange in an established rat model for surfactant deficiency. 3 Surfactant deficiency was induced in ventilated rats by repeated lavage of the lung with warm saline until P ao 2 dropped below 80 cmH 2 O with 100% inspired oxygen at standard ventilation settings. Subsequently an antibiotic‐surfactant mixture, saline, air, or surfactant alone was instilled intratracheally (4 ml kg −1 volume, n = 6 per treatment) and blood gas values were measured 5, 30, 60, 90 and 120 min after instillation. 4 The results showed that minimal surface tensions of the mixtures were comparable to that of surfactant alone. In vivo P ao 2 levels in the animals receiving ceftazidime‐surfactant or pentamidine‐surfactant were unchanged when compared to the surfactant group. P ao 2 levels in animals receiving amphotericin B‐surfactant, amoxicillin‐surfactant or tobramycin‐surfactant were significantly decreased compared to the surfactant group. For tobramycin it was further found that P ao 2 levels were not affected when 0.2 m NaHCO 3 (pH = 8.3) buffer was used for suspending surfactant instead of saline. 5 It is concluded that some antibiotics affect the in vivo activity of a bovine pulmonary surfactant. Therefore, before using surfactant‐antibiotic mixtures in clinical trials, interactions between the two agents should be carefully evaluated.