Leishmanicidal activity of two canthin-6-one alkaloids, two major constituents of Zanthoxylum chiloperone var. angustifolium.

The crude alkaloidal extract of Zanthoxylum chiloperone stem bark exhibited in vitro activity against various strains of Leishmania ssp. at 100 microg/ml. Two active major constituents were isolated and identified as canthin-6-one and 5-methoxycanthin-6-one. The effect of these compounds was also tested in an in vivo assay using BALB/c mice infected with Leishmania amazonensis. The mice were treated for 5 weeks postinfection with these alkaloids by oral (14 days) or intralesional route (4 days) at 10 mg/kg daily. The reference drug, N-methylglucamine antimonate was administered by subcutaneous injections at 100 mg/kg for 10 days. Intralesional administration of canthin-6-one reduced the parasite burden but not significantly when it was compared with the untreated group, while the reference drug reduced by 91% the parasite loads in the lesion.

[Statutory pediatric informations available for anticancer drugs: inventory and proposals]. / Autorisation de mise sur le marché et information pédiatrique pour les médicaments de chimiothérapie des cancers: état des lieux et propositions.

UNLABELLED: Paediatric medicines are often prescribed off label because appropriate clinical and pharmacological studies have not been conducted in children. A European directive is being written to promote the development of paediatric medicines through incentives to pharmaceutical companies, as is already the case in the US. METHOD: In order to evaluate the status of anticancer drugs, we analyzed the paediatric information available in the Vidal 2000 dictionary for cytotoxic chemotherapy. RESULTS: Among the 76 products, 48 were currently used to treat children with cancer. An indication for paediatric use was described in only 29% of them. Paediatric use was mentioned in the posology chapter in 56% of cases, and in the warning or contra-indication chapter in 17% of cases. Ten products (21%) were devoid of paediatric information. DISCUSSION: The paucity of this official paediatric information contrasts with the number of clinical and pharmacological studies that have been conducted and published by paediatric oncology societies and groups. Indeed, almost 80% of children with cancer are treated using prospective therapeutic research protocols. In conclusion, anticancer medicines have been evaluated in children, but official paediatric information is poor. This situation can be significantly improved with the literature currently available. On the other hand, prospective clinical studies are needed to better define the optimal dose in children under one year of age, to evaluate long-term sequelae in cured patients and to provide appropriate galenic forms for oral chemotherapy. CONCLUSION: Incentives are urgently needed to facilitate access to therapeutic innovations in oncology and their development in children with cancer.