Pharmacokinetic assessment of the monepantel plus oxfendazole combined administration in dairy cows.

Monepantel (MNP) is a novel anthelmintic compound launched into the veterinary pharmaceutical market. MNP is not licenced for use in dairy animals due to the prolonged elimination of its metabolite monepantel sulphone (MNPSO2 ) into milk. The goal of this study was to evaluate the presence of potential in vivo drug-drug interactions affecting the pattern of milk excretion after the coadministration of the anthelmintics MNP and oxfendazole (OFZ) to lactating dairy cows. The concentrations of both parent drugs and their metabolites were measured in plasma and milk samples by HPLC. MNPSO2 was the main metabolite recovered from plasma and milk after oral administration of MNP. A high distribution of MNPSO2 into milk was observed. The milk-to-plasma ratio (M/P ratio) for this metabolite was equal to 6.75. Conversely, the M/P ratio of OFZ was 1.26. Plasma concentration profiles of MNP and MNPSO2 were not modified in the presence of OFZ. The pattern of MNPSO2 excretion into milk was also unchanged in animals receiving MNP plus OFZ. The percentage of the total administered dose recovered from milk was 0.09 ± 0.04% (MNP) and 2.79 ± 1.54% (MNPSO2 ) after the administration of MNP alone and 0.06 ± 0.04% (MNP) and 2.34 ± 1.38% (MNPSO2 ) after the combined treatment. The presence of MNP did not alter the plasma and milk disposition kinetics of OFZ. The concentrations of the metabolite fenbendazole sulphone tended to be slightly higher in the coadministered group. Although from a pharmacodynamic point of view the coadministration of MNP and OFZ may be a useful tool, the presence of OFZ did not modify the in vivo pharmacokinetic behaviour of MNP and therefore did not result in reduced milk concentrations of MNPSO2 .

[3 multicenter phase II studies of the treatment of small cell bronchogenic carcinoma (incl. AIO studies BI + BII)]. / Drei multizentrische Phase-II-Studien in der Behandlung des kleinzelligen Bronchialkarzinoms (incl. AIO-Studien BI + BII).

Between March 1979 und January 1983 122 patients with small-cell carcinoma of the lung were treated with different polychemotherapy regimen. 33 patients received VP-16-213 (etoposid), ifosfamide and vindesine (VPIV). 37 patients were treated with adriamycin, cisplatin and vincristine (APO). A third 3-drug combination, cyclophosphamide, methotrexate and CCNU (CMCC), was given to the remaining 52 patients alternating with the two other regimen. Response rates varied between 61% for the APO regimen and 85% for the VPIV regimen. The median survival was 10 months for patients treated with VPIV or APO and 12 months for patients treated with alternating drug combinations. This difference was not statistically significant. The rate of long-term survivors (longer than 2 years after diagnosis) was 9.9%. Side effects were seen more frequently in the group treated with APO.