Influence of Pneumocystis carinii pneumonia on serum and tissue concentrations of pentamidine administered to rats by tracheal injections.
Pentamidine isethionate was administered by the tracheal route to control rats and immunodepressed rats with Pneumocystis carinii pneumonia (PCP). The serum concentration of pentamidine base 20 min after the administration was higher in the PCP rats (309 +/- 165 ng/ml) than in the control animals (71 +/- 36 mg/ml; p less than 0.001); 90 min after the injection the proportion of the pentamidine administered was lower in the right lung of the PCP rats (29 +/- 15%) than in the control rats (57 +/- 23%; p = 0.038); the proportion of pentamidine in the left kidney was higher in the PCP rats (14 +/- 4%) than in the control animals (4 +/- 2%; p less than 0.001). Respiratory clearance of 99mTc-DTPA, an index of the permeability of the respiratory epithelium, was higher in the PCP rats (1.84 +/- 0.42 %/min) than in the controls (0.44 +/- 0.11 %/min; p less than 0.001). We conclude that the more rapid diffusion of pentamidine from the alveolar lumen to the pulmonary circulation is explained by the increased alveolocapillary permeability as a result of pneumocystosis.
Mordelet-Dambrine
M
M
Université de Paris René Descartes, Service de Pneomologie, Hôpital Ambroise Paré, Boulogne, France.
Danel
C
C
Farinotti
R
R
Urzua
G
G
Barritault
L
L
Huchon
G J
GJ
D000704:Analysis of Variance; D000818:Animals; D015824:Blood-Air Barrier / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002463:Cell Membrane Permeability / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D007267:Injections; D008297:Male; D010419:Pentamidine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014018:Tissue Distribution; D014132:Trachea
D010419:Pentamidine