Melanin In The Photoprotection Of Skin

Melanin can absorb electrons, as has been observed for some cation-exchange polymers, and its ion-exchange activity plays an important role in the biological system when skin is exposed to sunlight or ionizing radiation (241). Studies on this characteristic property of melanin by different authors revealed the mechanism of photoprotection and broadened our knowledge regarding melanin color. The absorption spectra of both the eu- and phaeomelanins throughout the UV and visible range, show a...

Other Combination Chemotherapy Trials

The combination of irinotecan and raltitrexed was evaluated in two Phase I studies, whereby asthenia was found as the DLT in both studies. The recommended doses were irinotecan 350 mg m2 and raltitrexed 3 mg m2 once every 3 weeks (110,111). In v iro and n vivo studies have revealed synergism or additivity between irinotecan and cisplatin in numerous tumor cell lines and human tumor xenografts (112-120). The mechanism of interaction between both agents involves a delay by the topoisomerase I...

B dosefinding trials

Numerous Phase I clinical trials with topotecan in different schedules of drug administration have been performed (183). Based on the in vitro data on long-term exposure and the fact that efficacy of the drug has been demonstrated to be dependent on the schedules of administration, two schedules were selected for Phase II studies. Firstly, there is a 30-min i.v. infusion daily for 5 consecutive days every 3 weeks, at a dose of 1.5 mg m2 day. In this schedule, the DLT is short lasting,...

Considerations of Route of Administration

As mentioned earlier, cytotoxicity of topoisomerase I inhibitors increases with the duration of exposure. In vitro studies showed that short-term exposures to high concentrations are less effective than long-term exposure to low concentrations (29,30). Low-dose, prolonged exposure in vivo studies in animal models also resulted in less toxicity (242-246). On the other hand, in vitro and animal models have shown to be poor predictors of clinical efficacy and toxicity for several reasons,...

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...

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...

Info

In contrast, while it is toxic to insects such as H. zea, it did not show any tremorgenic effect in insects (64). 55 PenitremA 56 10-0-Acetylpenitrem A 55 PenitremA 56 10-0-Acetylpenitrem A 57 33,35,25,39-Tetrahydropenitrem A 58 Penitrem B 57 33,35,25,39-Tetrahydropenitrem A 58 Penitrem B Penitrem B was one of the penitrems isolated in the early 1970s and was reisolated as a congener of other penitrems in 1981 (57,65). It displayed a molecular formula of C37H45NO5 suggesting...