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Absorption of pyrvinium pamoate.

Pyrvinium pamoate, tablets and suspension, was administered as single 350-mg doses to 12 healthy male volunteers to determine whether there had been any systemic absorption. Six subjects received tablets and 6 received suspension on the first day; on day 8, subjects received the other dose form. Up to 4 days after administration there was no evidence of drug in blood and urine by spectroflorometric assay. Metabolic studies in rats showed minute quantities of drug in the liver and plasma but not of any metabolites.

Adult↗

DNA fluorescence induced by polymethine cation pyrvinium binding.

Pyrvinium is a polymethine cation which shows interesting fluorescence emission and DNA binding properties. In diluted aqueous solution, pyrvinium pamoate induced a bright yellow fluorescence in kinetoplast DNA from Trypanosoma cruzi epimastigotes as well as in chicken erythrocyte nuclei under a wide range of excitations. No fading was observed after mounting in suitable media. Spectroscopic studies on pyrvinium solutions revealed bathochromic and hypochromic shifts in the absorption spectrum of its complex with DNA. A striking enhancement of pyrvinium fluorescence was found in solvents of high viscosity or after binding to DNA. Experimental results and the chemical structure of pyrvinium allow us to suggest that the minor groove of adenine-thymine DNA regions could be the specific binding site for this new DNA fluorochrome.

Animals↗

The detection of chemical impurities by high pressure liquid chromatography and the genetic activity of medical grades of pyrvinium pamoate in Saccharomyces cerevisiae and Salmonella typhimurium.

The genetic activity of several medical grades of the anthelmintic drug pyrvinium pamoate, which is a dipyrvinium salt, was studied in a diploid mitotic recombination and gene conversion assay (strain D5 of Saccharomyces cerevisiae), and in several haploid yeast reversion assays (strains XV185-14C, XY718-1A, and 7854-1A). All of the samples were recombinogenic in strain D5 and mutagenic in the haploid strains, however, the degree of genetic activity varied considerably among the medical grades of pyrvinium pamoate that were tested. Similarly, these samples varied in degree of mutagenicity when they were tested in strains TA97, TA98, TA100, and TA102 of Salmonella typhimurium, but some of the medical grades of pyrvinium pamoate were mutagenic both in the presence and in the absence of the metabolic transformation system, whereas other medical grades of the drug required such activation to be mutagenic. In addition, the medical grades and dosage forms of several brands of pyrvinium pamoate were examined for purity by fluorescence high pressure liquid chromatography (HPLC) using a methanol:water (90:10) solvent system. The HPLC data indicate that monopyrvinium salts are the major contaminants in these pharmaceuticals. In general, there is a correlation between the degree of genetic activity and toxicity, and the number and relative quantity of impurities found in each sample.

Animals↗

Impaired intestinal electrolyte transport in rats infested with the common parasite Syphacia muris.

An incidentally discovered infestation with the nematode Syphacia muris of cecum and colon in spontaneously hypertensive (SHR) and normotensive control (WKY) rats was investigated over a two-year period. Infestation rates in WKY were higher than in SHR, while clinical signs as well as histological changes of colonic tissues were absent in both strains. In vivo net water absorption (microliter/hr/cm2) in control worm-free SHR turned into secretion in infested rats, ie, from 74.2 +/- 23.2 to -7.5 +/- 35.0 (P less than 0.001); this corresponded with a decrease in net absorption (mumol/hr/cm2) of Na from 18.5 +/- 2.4 to 9.3 +/- 4.3 (P less than 0.001) and of Cl from 14.0 +/- 3.2 to 3.2 +/- 5.7 (P less than 0.001). In WKY, net water absorption decreased from 112.2 +/- 23.2 to 48.0 +/- 25.1 (P less than 0.001) and Na and Cl absorption from 22.3 +/- 3.1 to 16.0 +/- 4.2 (P less than 0.005) and from 19.4 +/- 2.7 to 10.9 +/- 4.7 (P less than 0.005), respectively. Antihelminthic treatment with 0.007% pyrvinium pamoate in the ration (four weeks on, six months off) eradicated Syphacia muris in both rat strains. Body weight gain of young rats on normal and pyrvinium pamoate-substituted diet studied over 18 months was similar, indicating a good tolerance of the treatment. It is concluded that results obtained during comparative intestinal transport studies between SHR and WKY may not only be impaired but also significantly distorted by Syphacia muris infestation as SHR appear to be more susceptible to effects induced by this common parasite than WKY.

Animals↗

Study of the laxative properties of the disodium salt of the sulfuric diester of 3,3-bis-(4-hydroxyphenyl)-7-methyl-2-indolinone (DAN-603 in the rat.

The influence of DAN-603 (disodium salt of sulphuric diester of 3,3-bis-(4-hydroxyphenyl)-7-methyl-2-indolinone) on the propulsive motility of the rat digestive tract was studied by means of indicators (charcoal and pyrvinium pamoate) and radioactive tracers (133BaSO4). The results showed that DAN-603 increases selectively the colon motility without modifying the speed of gastric, intestinal (small intestine) and caecal emptying.

Animals↗

Pyrvinium pamoate lacks in vivo genotoxicity in the colon.

Pyrvinium pamoate, a widely used anthelmintic drug, has been previously tested for genotoxicity with equivocal results. Assays with bacterial or yeast test strains yielded positive results while in vitro tests with mammalian cells yielded negative results. In this study, the genotoxicity of pyrvinium was studied in vivo in the mouse colon, the therapeutic site of action of this agent. 1,2-Dimethylhydrazine (DMH), a colon carcinogen, was tested simultaneously as a positive control. The colonic nuclear aberration assay was used to determine genotoxicity. Pyrvinium delivered orally in three vehicles was not genotoxic in the murine colon, even at doses up to 12.5 times the recommended human dosage.

1,2-Dimethylhydrazine↗

Genetic activity in Saccharomyces cerevisiae and thin-layer chromatographic comparisons of medical grades of pyrvinium pamoate and monopyrvinium salts.

The pamoate, chloride, and iodide salts of pyrvinium, a cyanine dye with anthelmintic properties, were studied in a diploid mitotic recombination and gene conversion assay system (strain D5 of Saccharomyces cerevisiae) and a haploid yeast reversion assay (strain XV185-14C). With the use of a thin-layer chromatographic (TLC) detection technique, samples of pyrvinium pamoate from several sources were found to contain different numbers and quantities of impurities. All samples of pyrvinium pamoate and the monopyrvinium salts were recombinogenic in strain D5 and mutagenic in strain XV185-14C; the degree of genetic activity varied among the tested medical grades of pyrvinium pamoate. Monopotassium pamoate was found to be genetically inactive in both strains. Light-catalyzed degradation did not enhance the genetic activity of pyrvinium in either of the yeast strains; the degraded samples were not mutagenic.

Chromatography, Thin Layer↗

Genotoxicity of amebicide and anthelmintic drugs in Escherichia coli pol A+/pol A-.

The amebicides dehydroemetine and chloroquine diphosphate and the anthelmintic pyrvinium pamoate, previously reported to be mutagenic in Salmonella typhimurium (Cortinas de Nava et al., 1983), were clearly shown to be genotoxic in the Escherichia coli pol A+/pol A- assay. Two other antiparasitic drugs, diiodohydroxyquin and 4-hexylresorcinol, were also found to be genotoxic in E. coli, while iodochlorhydroxyquin preferentially inhibited the pol A+ strain. From the 3 alternative testing methods employed, the liquid suspension succeeded in detecting 5 antiparasitic drugs as genotoxic; the microsuspension identified 2, and the disc diffusion method only 1. However, the metabolic activation system could only be coupled successfully and in a reproducible way to the microsuspension assay.

Amebicides↗

A comparison of the genetic activity of pyrvinium pamoate with that of several other anthelmintic drugs in Saccharomyces cerevisiae.

Several anthelmintic drugs that are used routinely in oxyuriasis therapy were analyzed for genotoxicity in a diploid mitotic recombination and gene conversion assay (strain D5 of Saccharomyces cerevisiae), and in a haploid yeast reversion assay (strain XV185-14C). Piperazine citrate, piperazine adipate, mebendazole and thiabendazole did not appear to be genotoxic in either yeast strain. Pyrvinium pamoate induced the reversion of the missense, nonsense and frameshift alleles in strain XV185-14C, whereas pyrantel pamoate induced only the reversion of the frameshift allele. Pyrvinium pamoate was recombinogenic in strain D5, and there is an indication that pyrantel pamoate, at the lowest dose that was tested, might induce gene conversion or aneuploidy.

Anthelmintics↗

Application of enzyme immunoassay for postchemotherapy evaluation of human strongyloidiasis.

Posttherapy evaluation of strongyloidiasis is frequently difficult because coprologic examination is not sensitive enough for diagnosis of chronic infection. In the present study, anti-Strongyloides enzyme-linked immunosorbent assay antibodies were monitored before and after treatment with thiabendazole and pyrvinium pamoate in 199 patients with chronic strongyloidiasis in Okinawa, Japan. A significant decrease in antibody levels was observed in patients who became negative for fecal larvae after the treatment, whereas the antibody levels did not show a significant change after the treatment in patients who were still harboring the parasite. In the group coprologically negative in the follow-up examination, however, many individuals did not show a significant fall in antibody titers after treatment, which suggests that these cases were equivocal for complete cure. By the subsequent fecal reexamination performed on the equivocal cases, approximately 20% were additionally found to be still harboring the parasite. These results indicate that serologic testing is useful to check whether a real cure has been achieved among the patients in whose fecal samples the presence of larvae has not been demonstrated after treatment.

Adult↗