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Intestinal alkalization as a possible preventive mechanism in irinotecan (CPT-11)-induced diarrhea.

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The therapeutic efficacy of irinotecan (CPT-11), a DNA topoisomerase inhibitor, is often limited by the induction of severe late-onset diarrhea. This prodrug and its active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN-38), have a labile alpha-hydroxy-lactone ring that undergoes pH-dependent

Saccharic acid 1.4-lactone protects against CPT-11-induced mucosa damage in rats.

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OBJECTIVE To evaluate the ability of D-saccharic acid 1.4-lactone (SAL), a beta-glucuronidase inhibitor, to prevent irinotecan hydrochloride (CPT-11) from inducing mucosal damage as a cause of diarrhea in rats. METHODS Wistar rats were divided into six groups of three animals each, administered 1.0

Sesquiterpene lactones from the aerial parts of Vernonia blumeoides growing in Nigeria.

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Four eudesmanolide sesquiterpene lactones (1-4) were isolated from the aerial parts of Vernonia blumeoides used in Nigerian ethnomedicine for the treatment of diarrhea and malaria. Compound 1 demonstrated limited but interesting antibacterial activity against Bacillus, Staphylococcus and

Excretion into gastrointestinal tract of irinotecan lactone and carboxylate forms and their pharmacodynamics in rodents.

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OBJECTIVE To investigate the excretion of irinotecan hydrochloride (CPT-11) and its active metabolite, SN-38, into the gastrointestinal lumen via the biliary and/or intestinal membrane route after dosing with lactone and carboxylate forms of CPT-11, and to evaluate the toxic and antitumor effects of

SdiA sensing of acyl-homoserine lactones by enterohemorrhagic E. coli (EHEC) serotype O157:H7 in the bovine rumen.

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Chemical communication mediates signaling between cells. Bacteria also engage in chemical signaling, termed quorum sensing (QS), to coordinate population-wide behavior. The bacterial pathogen enterohemorrhagic E. coli (EHEC), responsible for outbreaks of bloody diarrhea worldwide, exploits QS to

Sesquiterpenoids lactones: benefits to plants and people.

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Sesquiterpenoids, and specifically sesquiterpene lactones from Asteraceae, may play a highly significant role in human health, both as part of a balanced diet and as pharmaceutical agents, due to their potential for the treatment of cardiovascular disease and cancer. This review highlights the role

DX-8951f: summary of phase I clinical trials.

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Exatecan mesylate (DX-8951f) is a new hexacyclic camptothecin analogue with favorable attributes compared to topotecan and CPT-11, including watersolubility, greater potency against topoisomerase I, lack of esterase-dependent activation, broad antitumor activity, and low cross-resistance against

Safety evaluation of orally administered afoxolaner and milbemycin oxime in eight-week-old dogs.

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The safety profile of afoxolaner (an isoxazoline molecule) when combined with milbemycin oxime (a macrocyclic lactone) was evaluated according to the regulatory requirements when administered six times orally in a soft chewable formulation at a dose of at least 1×, 3×, or 5× the maximum exposure

Regulation of virulence factors of enterohemorrhagic Escherichia coli O157:H7 by self-produced extracellular factors.

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Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes serious diarrhea and hemolytic uremic syndrome in humans. The expressions of EspD and intimin by O157:H7 have now been shown to be down-regulated by medium conditioned by O157:H7 grown at stationary phase. Preparation of conditioned medium

Altered pharmacokinetics and metabolism of CPT-11 in liver dysfunction: a need for guidelines.

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Metabolic conversion of CPT-11 is a major route of elimination of this new topoisomerase 1 inhibitor. Presently, recommendations for dose adjustments of CPT-11 in patients with liver dysfunction are lacking. We describe the case of a patient with metastatic colon cancer with liver dysfunction

Phase I and pharmacological study of a new camptothecin derivative, exatecan mesylate (DX-8951f), infused over 30 minutes every three weeks.

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OBJECTIVE A Phase I study of exatecan, a new water-soluble camptothecin derivative, was conducted to determine the maximum tolerated dose and a recommended dose, according to an internationally standardized core protocol. Pharmacological profiles of lactone and total (lactone + carboxylate) exatecan

A phase I study of 9-aminocamptothecin as a colloidal dispersion formulation given as a fortnightly 72-h infusion.

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OBJECTIVE A phase I pharmacologic study was undertaken to determine the maximum tolerated dose (MTD), to characterize the pharmacokinetic profile, and to evaluate all toxicities of the aqueous colloidal dispersion formulation of 9-aminocampothecin (9-AC). METHODS 9-AC was administered as a constant

Metabolism of irinotecan and its active metabolite SN-38 by intestinal microflora in rats.

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One of the dose-limiting toxicities of irinotecan (CPT-11) is delayed-onset diarrhea, which is the greatest barrier to treatment with CPT-11-containing regimens. CPT-11 is converted to its active metabolite, SN-38, which is conjugated by hepatic uridine diphosphate glucuronosyl transferase to SN-38

Whole-Genome Analysis of Aeromonas hydrophila Strain 187, Exhibiting Quorum-Sensing Activity.

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Aeromonas hydrophila is a quorum-sensing (QS) bacterium that causes diarrhea in humans upon infection. Here, we report the genome of pathogenic Aeromonas hydrophila strain 187, which possesses a QS gene responsible for signaling molecule N-acyl homoserine lactone (AHL) synthesis and has been found

Pharmacokinetic changes of irinotecan by intestinal alkalinization in an advanced colorectal cancer patient.

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The prevention of irinotecan (CPT-11)-induced diarrhea, a well-known adverse reaction to the drug, by treatment with intestinal alkalinization has been carried out in patients with colorectal cancer in Japan. Under acidic conditions, CPT-11 and its active metabolite, SN-38, exists preferably as the

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