Clinical Pharmacology

Topotecan (TPT is a semisynthetic, water-soluble CPT derivative, synthesized by modification of 10-hydroxycamptothecin (155). It undergoes CYP3A-catalyzed metabolism to N-desmethyl topotecan. N-Desmethyl topotecan is a less-active metabolite of which only low plasma levels were found, suggesting minimal CYP3A-related conversion. Nonetheless, clinical trials have shown significantly altered clearance of topotecan in patients on CYP3A-inducing anticonvulsants, similar to that observed with...

Info

Proposed biogenetic pathway for the indole diterpenoids (10,35). Scheme 25. Proposed biogenetic pathway for the indole diterpenoids (10,35). and 10ft-hydroxy-13-desoxypaxilline (24) (Scheme 25). In consideration of the structural range of indole-diterpenoid alkaloids thus far described from Acremonium, Aspergillus, Claviceps, and Penicillium, the authors generated a scheme describing the putative biosynthetic relationships of some of these alkaloids. This scheme was later modified by...

Index

Note Page numbers followed by f or t refer to the figure or table on that page, respectively. Acanthostrongylophora sp., 215, 216t, 219, 222, 259, 260, 261, 263, 264, 276 Acanthothamine, 307t Acanthothamnus aphyllus, 335t 26-ep -10-O-Acetyllolitrem N isolation, 107-108 properties, 61 27-O-Acetylpaxilline isolation, 67 properties, 56 10-O-Acetylpenitrem A, 88 Acremonium lolii, 65, 68 Acremonium sp., 52, 104, 149 Adenocarcinoma, 333 Adverse effects. see Side effects Aedes aegypti, 121 J-Aflatrem...

Antitumor Efficacy

The dosage regimen of topotecan approved for clinical use is 1.5 mg m2 day given as a 30-min i.v. infusion daily for 5 days every 3 weeks. Dose-related, reversible, and noncumulative myelosuppression is the most important side effect of topotecan (229). Neutropenia - the nadir is usually approximately 9 days after the start of the treatment and the median duration is approximately 7-10 days - occurred more frequently and is often more severe than thrombocytopenia. Also, neutropenia was more...

Melanin

Metal cations and organic species carrying positive charge(s), possess a strong affinity to melanins, and binding occurs through an ion-exchange mechanism. This characteristic phenomenon has been studied by different authors to explain the medicinal aspects which may involve affinity and binding of various molecules to melanins in substantia nigra, in malignant melanoma cells, and in the toxicity of drugs. For example, a pathological pigmentation often occurs in the skin of the patients taking...

A 9substituted camptothecins

9-Aminocamptothecin (9-AC) is a semisynthetic CPT derivative which showed outstanding preclinical activity against a wide spectrum of tumor types, including those of breast, colon, lung, prostate, and melanoma (255). In clinical trials, the drug has been very extensively studied using two different formulations based on the use of dimethylacetamide polyethylene glycol 400 or a colloidal dispersion preparation, which enhances solubility and stability. Clinical Phase I investigations have been...