ABSTRACT
Our study has shown that after single administration of its substance or its polymer formulation, medamine rapidly absorbs into blood, by penetrating into the host's viscera and tissues and parasitic larvocysts and excretes from the experimental animals' body at hour 24. Examining the distribution of medamine in the viscera and tissues has revealed that it penetrates into the rat viscera and tissue with blood and accumulated in the tissues. At the same time medamine given as a substance accumulates more in the excretory organs and medapec retains in the muscle tissue and brain longer. Medapec shows higher maximum concentrations at lower values of the pharmacokinetic curve area. Noticeable accumulation of medamine in the larvocysts of experimental animals confirms its chemotherapeutical activity.
Subject(s)
Anticestodal Agents/pharmacokinetics , Benzimidazoles/pharmacokinetics , Carbamates , Echinococcosis, Hepatic/metabolism , Sigmodontinae , Administration, Oral , Animals , Anticestodal Agents/administration & dosage , Anticestodal Agents/analysis , Benzimidazoles/administration & dosage , Benzimidazoles/analysis , Chromatography, High Pressure Liquid , Drug Evaluation, Preclinical , Echinococcosis, Hepatic/drug therapy , Male , Time Factors , Tissue DistributionABSTRACT
The paper describes a procedure for manufacturing the new anthelminthic Tizanox. It shows it necessary to administer a larger dose of the drug than that of azinox (praziquantel) to treat experimental hymenolepiasis. However, the lower toxicity of Tizanox enhances its chemotherapeutical index.
Subject(s)
Anticestodal Agents/chemical synthesis , Anticestodal Agents/therapeutic use , Hymenolepiasis/drug therapy , Isoquinolines/chemical synthesis , Isoquinolines/therapeutic use , Thiadiazines/chemical synthesis , Thiadiazines/therapeutic use , Animals , Anticestodal Agents/analysis , Anticestodal Agents/toxicity , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Isoquinolines/analysis , Isoquinolines/toxicity , Mice , Praziquantel/analogs & derivatives , Praziquantel/therapeutic use , Praziquantel/toxicity , Spectrophotometry, Infrared/statistics & numerical data , Thiadiazines/analysis , Thiadiazines/toxicityABSTRACT
Data transformations and weighting schemes are normally used to obtain the best-fit of standard curves in bioanalysis and the calibration model is usually selected during prevalidation. In the present study, a comparison has been made between unweighted and weighted (1/x, 1/x2, and 1/square root of x) regression models with or without an intercept in achieving the best-fit for the standard curve of CDRI compound 81/470, a new anthelmintic agent, in cow milk. Validation samples in milk at the LLOQ, medium, and high concentrations were also analysed by each of the calibration models. An unweighted regression equation with an intercept overestimated the concentrations at the LLOQ. An unweighted equation without intercept and weighted equations with or without an intercept significantly minimized the bias at the LLOQ without distorting the results at higher concentrations. Hence, an unweighted equation for a straight line passing through the origin was found to be the best model for a standard curve of 81/470 in milk. Similar results were obtained for 81/470 and UMF-078 in serum and plasma, respectively. Bioanalysts should routinely test these models to obtain the best fit model for their calibration curves as part of their assay validation not during prevalidation.
Subject(s)
Anticestodal Agents/analysis , Benzimidazoles/analysis , Carbamates/analysis , Chromatography, High Pressure Liquid/standards , Models, Chemical , Animals , Anticestodal Agents/blood , Benzimidazoles/blood , Calibration/standards , Carbamates/blood , Cattle , Evaluation Studies as Topic , Female , Linear Models , Melphalan/analogs & derivatives , Melphalan/analysis , Milk/chemistry , Reproducibility of ResultsABSTRACT
CDRI compound 81/470 is a new broad spectrum anthelmintic agent and is being developed for veterinary use. HPLC assay method for 81/470 in cow milk was developed and validated. The sample preparation consisted of protein precipitation, followed by extraction with ether. Separation was achieved on a C18 column using acetonitrile-buffer (pH 6, 50 mM) mobile phase and the compound was quantitated using fluorescence detector. The recovery of 81/470 was above 90% and was consistent over the calibration range of 10-1000 ng ml-1. Accuracy and precision were determined by analyzing replicate samples and were found to be within acceptable limits. Five freeze-thaw cycles of spiked milk and storage of processed dry residues at -30 degrees C for 7 days did not have any detrimental effect on the stability of 81/470.
Subject(s)
Anticestodal Agents/analysis , Benzimidazoles/analysis , Carbamates/analysis , Milk/chemistry , Animals , Chromatography, High Pressure Liquid , Drug Stability , Reproducibility of ResultsABSTRACT
A procedure has been developed to manufacture the anthelminthic Triclonate. The agent was tested for the treatment of sheep's natural monieziasis infection and it was found to have a high activity.