PT  - JOURNAL ARTICLE
AU  - H Foth
AU  - J Hellkamp
AU  - E M Kunellis
AU  - G F Kahl
TI  - Pulmonary elimination and metabolism of 5-fluoro-2'-deoxyuridine in isolated perfused rat lung and lung slices.
DP  - 1990 Nov 01
TA  - Drug Metabolism and Disposition
PG  - 1011--1017
VI  - 18
IP  - 6
4099  - http://dmd.aspetjournals.org/content/18/6/1011.short
4100  - http://dmd.aspetjournals.org/content/18/6/1011.full
SO  - Drug Metab Dispos1990 Nov 01; 18
AB  - Elimination kinetics and metabolism of the cytostatic drug 5-fluoro-2'-deoxyuridine (FUDR) were studied in isolated perfused rat lung and in incubated lung slices. The intact organ exhibited a low clearance of 0.2 to 0.8 ml/min and a calculated first-pass extraction of 2 to 7% of the drug inflow. Thus, the pulmonary uptake of the fluorinated nucleoside from the circulation is low. Within 120 min of perfusion, however, 30 to 45% of the initial FUDR dose was metabolized by the isolated rat lung. The nucleobase metabolite 5-fluorouracil (FU) represented almost all FUDR metabolites in the medium, indicating that this metabolic pathway, mediated by thymidine phosphorylase, is active in lung while the enzymic activity for further pyrimidine degradation is low. This was demonstrated in incubated lung slices, which have a high capacity to transform FUDR into FU, comprising 83 to 95% of the metabolites in the medium. The final catabolic metabolite, alpha-fluoro-beta-alanine, was present in trace amounts only. It is concluded that the pulmonary tissue contains a marked "intrinsic" capacity to transform FUDR into FU, while the metabolic activity for catabolism of the nucleobase metabolites FU and 5,6-dihydrouracil is virtually lacking.