Effect of Azotemia in Dogs on the Pharmacokinetics of Pentamidine

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Abstract
We used a new high-performance liquid-chromatography assay to study the pharmacokinetics of pentamidine isethionate given intravenously to 10 dogs before and after surgically induced renal failure. The presurgery peak serum concentration of pentamidine averaged 867 ng/ml and by 6 hr had fallen to 30 ng/ml. After surgery the peak and 6-hr concentrations were 780 ng/ml and 28 ng/ml. Mean total body clearance of pentamidine before surgery was 46.7 ml/min per kg, of which only 2.0 ml/min per kg was due to renal clearance. After surgery, total body clearance was 40.0 ml/min per kg, even though renal clearance had fallen 80%—to 0.4 ml/min per kg. Twodogs with azotemia and two control dogs received 14 daily infusions of pentamidine. Kinetic parameters measured after the last dose were not significantly different from those after the first dose, and the amount of pentamidine recovered from tissues was similar for dogs with azotemia and controls. In summary, because renal clearance of pentamidine accounted for such a small proportion of total body clearance, none of the parameters measured was affected significantly by moderate azotemia.

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