Tetracycline and erythromycin distribution in pathological lungs of humans and rat.
Tetracycline and erythromycin concentrate highly in pulmonary tissues in humans as well as in the rat. Their binding to the lung, whatever the species and the pathological state, is weak. Their intrapulmonary concentrations could be explained by a passive diffusion which depends on the pH variation between the intra- and extratissue compartments, the percentage of un-ionized form present, and their liposolubility. The importance of retention of tetracycline and erythromycin by plasma proteins is demonstrated by the decrease of their pulmonary index of penetration (IP, the intra- and extratissue concentrations ratio). The IP values are, respectively, 1.09 and 1.23 for tetracycline and erythromycin. These concentrations are in excess of their minimal inhibitory concentrations for bacteria responsible for pneumopathies. The lung homogenate binding of these antibiotics is weak (5% for erythromycin and 33% for tetracycline), corresponding to a nonsaturable binding to three main subcellular fractions (nucleus, mitochondria, and cytosol). Tetracycline has the same penetration in healthy or cancerous human lungs, whereas erythromycin presents a decreased IP in cancerous tissue. However, the binding of these antibiotics to healthy or cancerous lung homogenates is similar. So, the structure of cancerous cells is solely responsible for this modification of erythromycin penetration. The intrapulmonary concentration of tetracycline is increased in rat lungs infected by Legionella pneumophila. This modification is due to a great bacteria retention. In contrast, erythromycin possesses the same IP in healthy and infected rat lungs.
Fournet
M P
MP
Service de Pharmacologie, Faculté de Médecine de Paris XII, Créteil, France.
Zini
R
R
DeForges
L
L
Lange
F
F
Lange
J
J
Tillement
J P
JP
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D004917:Erythromycin / Q000493:pharmacokinetics*; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D007877:Legionnaires' Disease / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008171:Lung Diseases / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013056:Spectrophotometry, Ultraviolet; D013347:Subcellular Fractions / Q000378:metabolism; D013752:Tetracycline / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D001798:Blood Proteins; D004917:Erythromycin; D013752:Tetracycline