Autoradiographic examination of the organ distribution of 14C-labelled pentamidine in rats after intravenous and inhaled administration.
The organ distribution of 14C pentamidine was studied in Sprague Dawley rats by means of whole-body autoradiography following intravenous and inhaled application of pentamidine (Pentacarinat, CAS 140-64-7). The distribution time after intravenous administration of 5 mg pentamidine per kg rat was 30 min, 6 h, 24 h, and 7 days, respectively. The corresponding times after administration of aerosolized pentamidine were 30 min and 24 h. The distribution of radioactivity was also determined by measuring radioactivity in punch specimens of 100 microns sections. Besides renal excretion, the excretion of pentamidine in the bile and via the salivary glands was assessed by autoradiography. Further target organs included the spleen and the bone marrow. As early as after 30 min no radioactivity was detectable in the blood vessels. A lack of radioactivity in the brain tissue with accumulation of pentamidine in the meninges suggests that pentamidine does not cross the blood/brain barrier. Following intravenous administration the lung uptake of pentamidine was relatively low. However, increased drug concentrations were recorded in the bronchial system. The elimination time of pentamidine from the target organs was long. Lung pentamidine concentrations remained almost unchanged for a period of 7 days. After inhaled administration high levels of pentamidine were measured in the lung. 14C pentamidine was also located in the oropharyngeal and gastrointestinal tract, the drug stemming from pentamidine ingested or licked off the skin by the animals. No further target organs were verifiable. From the pharmacological point of view, these studies prove the advantages of pentamidine aerosol in the treatment of Pneumocystis carinii pneumonia (PCP) and provide information on extrarenal excretion mechanisms and deep compartments.
Wingen
F
F
Clinical Research Department, Rhône-Poulenc Rorer GmbH, Cologne, Fed. Rep. of Germany.
Brägas
B
B
D000280:Administration, Inhalation; D000818:Animals; D001345:Autoradiography; D007275:Injections, Intravenous; D008297:Male; D010419:Pentamidine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D010419:Pentamidine