Disease relevance of Phenthiourezine

• An open clinical trial of amocarzine was carried out in onchocerciasis patients in Ecuador and Guatemala [1].
• Twenty-eight patients who had skin snips positive for microfilariae (Mf) were studied 120 days after receiving amocarzine, when each was negative for Mf: 16 (57%) were positive for O. volvulus DNA in the PCR-based assay [2].
• The clinical investigations with three types of a three days regimen of amocarzine permitted to adjust the fixed dosing to the body weight related dosing and subsequently the administration of amocarzine from fasting state to drug intake after food [3].

High impact information on Phenthiourezine

• The administration of CGP 6140 after food intake is therefore recommended for an optimal systemic effect [4].
• Pharmacokinetics of CGP 6140 (amocarzine) after oral administration of single 100-1600 mg doses to patients with onchocerciasis [5].
• The low solubility of CGP 6140 in aqueous solutions at neutral pH and its higher solubility at acidic pH might explain the increase in bioavailability after food intake [4].
• Mean (+/- s.d.) AUC CGP 6140 values were 67.0 +/- 10.8 mumol l-1 h in fed and 22.0 +/- 17.2 mumol l-1 h in fasting patients [4].
• Immunoelectron microscopic evidence for release of eosinophil granule matrix protein onto microfilariae of Onchocerca volvulus in the skin after exposure to amocarzine [6].

Chemical compound and disease context of Phenthiourezine

• Electron microscopic studies on the effects of CGP 6140 and CGP 20376 on microfilariae and third stage larvae of Onchocerca volvulus [7].

Biological context of Phenthiourezine

• The influence of food on the pharmacokinetics of CGP 6140 (amocarzine) after oral administration of a 1200 mg single dose to patients with onchocerciasis [4].
• Vacuolization before mitochondrial swelling was observed only after treatment with CGP 6140 [8].
• Modulatory effects of antifilarial drugs ivermectin, CGP 6140 and CGP 20376 on the oxidative burst of eosinophilic granulocytes [9].
• Conversely, the concentrations of amocarzine in fed patients after 150 and 1200 mg were dose proportional, thus indicating linear kinetics [10].
• High doses of CGP 6140 had only unsatisfactory effects on the larvae in this model system whereas CGP 20376 had inhibited moulting and killed most larvae with a daily dose of 25 mg/kg for five consecutive days [11].

Anatomical context of Phenthiourezine

• In addition, the glandular esophagus demonstrated degenerative alterations of the cytoplasm and loosening of the cuticular lining after exposure to CGP 6140 [7].

Associations of Phenthiourezine with other chemical compounds

• Activity, mechanism of action and pharmacokinetics of 2-tert-butylbenzothiazole and CGP 6140 (amocarzine) antifilarial drugs [12].

Gene context of Phenthiourezine

• At 20-28 h after the application of amocarzine, mf were degenerated or dead and a marked eosinophil-parasite adherence (EPA) reaction was seen, with intense staining for intra- and extracellular eosinophil granule proteins such as eosinophil cationic protein (ECP) surrounding the mf [6].

Analytical, diagnostic and therapeutic context of Phenthiourezine

• Fully automated analytical system using liquid-solid extraction and liquid chromatography for the determination of CGP 6140 in plasma [13].
• CGP 6140 is currently undergoing clinical trials in patients suffering from onchocercosis [12].
• Ultrasonography of onchocercal skin nodules detected changes within the nodules following amocarzine therapy [3].
• Since amocarzine and its major N-oxide metabolite are coloured agents, urine colorimetry was used to assess the urinary excretion of the N-oxide qualitatively [14].
• The present results indicate that an ophthalmologic real time linear scanner can be used in the bidimensional mode as a non-invasive method to assess sequentially the events in superficial onchocercal nodules following chemotherapy with amocarzine [15].

References