[Pharmacokinetics of a new antitumor antibiotic, neothramycin, after intrapleural administration]

In 5 patients with malignant pleural effusion, neothramycin (NTM) was intrapleurally administered at a dose of 30 mg in 3 cases and 40 mg in 2 cases and the pharmacokinetics was studied by using compartment models. The results were as follows: 1) Pleural levels of NTM were described by a mono-exponential equation and the half-life ranged from 3.45 to 6.48 hr. 2) The time to reach the maximum plasma level was 1 to 2 hr after pleural administration. The maximum levels were 54 to 106.4 ng/ml with the 30 mg dosage and 74.7 to 79.2 ng/ml with the 40 mg dosage, followed by a slow decline, with T1/2 ranging from 6.54 to 17.80 hr. 3) The elimination half-life of NTM in the plasma after intrapleural administration was much longer than that after intravenous administration. This phenomenon can be explained by a "flip-flop model": in this case, the rate of transfer from the pleural space to the plasma was much slower than that of the elimination from the plasma. 4) The parameters, K1 and K2, which were obtained by the deconvolution method, seemed to reflect the transfer of NTM between the pleural space and the plasma. 5) In 3 out of the 4 evaluable cases, an extreme decrease in the pleural fluid volume and suppression of reswelling were observed, including a case found to be negative for tumor cells upon cytodiagnosis.