Autoradiography study of organ distribution of 14C pentamidine following intravenous and inhalational administration in rats


Wingen, F.

Medizinische Klinik 85 (Suppl. 2): 236-44, 291

1990


The organ distribution of 14C pentamidine was studied in Sprague Dawley rats by means of whole-body autoradiography following intravenous application and inhalation of aerosolized pentamidine. The distribution time after intravenous administration of 5 mg pentamidine per kg rat was 30 minutes, six hours, 24 hours, and seven days respectively. The corresponding times after administration of aerosolized pentamidine were 30 minutes and 24 hours. By measuring radioactivity in punch specimens of 100 microns sections, the distribution of radioactivity could also be determined semiquantitatively. 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 minutes no radioactivity was detectable in the blood vessels. A lack of radioactivity in the brain tissue, with concentration of pentamidine in the meninges, suggests that pentamidine does not pass the blood/brain barrier. Following intravenous administration, the lung uptake of pentamidine was relatively low. However, increased drug levels were recorded in the bronchial system. The elimination time of pentamidine from the target organs was long. The lung levels of pentamidine remained almost unchanged for a period of seven days. Following application by inhalation, high levels of pentamidine were measured in the lung. 14C pentamidine was also detectable in the oropharyngeal and gastrointestinal tract, the drug stemming from pentamidine ingested or licked off the skin by the animals. Other target organs could not be demonstrated. From the pharmacological point of view, these studies prove the advantages of pentamidine aerosol in the treatment of pneumocystis carinii pneumonia and provide information on extrarenal excretion mechanisms and deep compartments.