Pharmacokinetics and metabolism of nilutamide in the isolated rat lung.

Abstract

Nilutamide (N) is a potent antiandrogen used in the treatment of diffuse carcinoma of the prostate. The drug has been implicated in a few instances of pneumonitis in man. The present studies were carried out to examine N disposition in the isolated perfused lung (IPL) from rats. Both recirculating and single-pass IPL were used. Recirculation was run for 60 min at concentrations of N ranging between 12 and 120 microM (+1 mu Ci [14C]N). Single-pass perfusions were run for 30 min (uptake, 10 min; efflux, 20 min) at inflowing concentrations ranging from 12 to 480 microM (+1 mu Ci [14C]N). Nilutamide was concentrated in the recirculating IPL, and tissue to medium ratio (T/M) ranged between 6.6 and 4.2, depending on the inflowing concentration of N (Cin). High performance liquid chromatography analysis of extracts of 60-min lung homogenates demonstrated the primary amino metabolite of N in addition to the parent compound. This indicated reduction of the nitro moiety of N by lung tissues. At 60 min and Cin = 40 microM, 17.6 +/- 4.7% of the radioactivity present in lung was accounted for by the metabolite. Perfusate samples contained low to undetectable amounts of the metabolite. No metabolism of N was detected in single-pass IPL, possibly because of the shorter duration of experiments. Amount of N taken up in lung and T/M were similar to those found in recirculating preparations. Uptake of N in the single-pass IPL was proportional to N concentration up to 480 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: P Camus, B Coudert, P D'Athis, P Foucher, J Delchambre, A Dupront, L Jeannin
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 259 Issue 3 Pg. 1247-55 (Dec 1991) ISSN: 0022-3565 [Print] United States
• PMID: 1762072 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgen Antagonists
• Imidazoles
• Imidazolidines
• nilutamide

Topics

• Androgen Antagonists (metabolism, pharmacokinetics)
• Animals
• Chromatography, High Pressure Liquid
• Female
• Imidazoles (metabolism, pharmacokinetics)
• Imidazolidines
• Lung (metabolism)
• Male
• Perfusion
• Rats
• Rats, Inbred Strains