Plasma concentrations and tissue residues of bicozamycin given orally to pigs.

Bicozamycin was dissolved in water and administered to pigs by stomach tube at 40 mg/kg once daily for 7 consecutive days. The plasma concentration was determined on days 1 and 7 of the dosing period. The mean (+/- SD) peak plasma concentrations were 2.06 +/- 0.36 micrograms/ml at 3.08 +/- 0.80 h on day 1 and 2.36 +/- 1.32 micrograms/ml at 2.80 +/- 0.74 h on day 7, the elimination half-lives being 3.80 +/- 0.92 h and 2.43 +/- 1.41 h, respectively. The mean areas under the plasma concentration-time curves were 15.88 +/- 2.18 (micrograms h)/ml on day 1 and 12.31 +/- 6.98 (micrograms h)/ml on day 7. These pharmacokinetic parameters did not differ between days 1 and 7, suggesting that there was no accumulation in the plasma after consecutive oral dosing. The residues in kidney, liver and muscle were examined in pigs slaughtered on days 1, 3 and 5 after the last dosing. One day after withdrawal, residues were found in the kidneys of all three pigs examined, at a mean concentration of 0.26 microgram/g, and in muscle from one pig, but not in liver from any of the pigs. Bicozamycin was not detected in any of the samples taken 3 or 5 days after withdrawal.