Oral Administration of Protease-Soluble Chicken Type II Collagen Ameliorates Anterior Cruciate Ligament Transection-Induced Osteoarthritis in Rats.

This study investigated whether oral supplementation with protease-soluble chicken type II collagen (PSCC-II) mitigates the progression of anterior cruciate ligament transection (ACLT)-induced osteoarthritis (OA) in rats. Eight-week-old male Wistar rats were randomly assigned to the following groups: control, sham, ACLT, group A (ACLT + pepsin-soluble collagen type II collagen (C-II) with type I collagen), group B (ACLT + Amano M-soluble C-II with type I collagen), group C (ACLT + high-dose Amano M-soluble C-II with type I collagen), and group D (ACLT + unproteolyzed C-II). Various methods were employed to analyze the knee joint: nociceptive tests, microcomputed tomography, histopathology, and immunohistochemistry. Rats treated with any form of C-II had significant reductions in pain sensitivity and cartilage degradation. Groups that received PSCC-II treatment effectively mitigated the ACLT-induced effects of OA concerning cancellous bone volume, trabecular number, and trabecular separation compared with the ACLT alone group. Furthermore, PSCC-II and unproteolyzed C-II suppressed ACLT-induced effects, such as the downregulation of C-II and upregulation of matrix metalloproteinase-13, tumor necrosis factor-α, and interleukin-1ß. These results indicate that PSCC-II treatment retains the protective effects of traditional undenatured C-II and provide superior benefits for OA management. These benefits encompass pain relief, anti-inflammatory effects, and the protection of cartilage and cancellous bone.

Pharmacokinetics and dose proportionality of oral moxidectin in beagle dogs.

PURPOSE: To study the pharmacokinetics and dose proportionality of moxidectin in beagle dogs experimentally infected with the filarial parasite Brugia pahangi, and to evaluate and compare the results obtained from population pharmacokinetic analysis and individual compartmental analysis. METHOD: Thirty-six infected dogs were selected and randomly allocated into six treatment groups of six dogs each. Doses of 250 or 1000 microg/kg were given orally. The plasma drug concentration-time data were analyzed by population compartmental and individual compartmental methods. RESULTS: The best pharmacokinetic model was a two-compartment model with first-order absorption. According to the results obtained from population compartmental analysis, moxidectin is a low clearance drug with a relatively high volume of distribution, resulting in a mean terminal half-life of 458 h. Absorption was rapid with a mean absorption half-life of 0.6 h and T(max) of 2.75 h. Significant weight effect was found on Vc. These results were compared with results obtained from individual compartmental approach. A statistically significant (p<0.01) gender difference in T1/2beta was observed with the 250 microg/kg dose, and a trend was observed with a greater T1/2beta in females at the 1000 microg/kg dose. No gender effect on other pharmacokinetic parameters was found. CONCLUSIONS: A pronounced distribution phase was observed and there was a significant weight effect on Vc. Dose proportionality of moxidectin was assessed by comparing the AUC (0-last determination) values for 250 and 1000 microg/kg. The pharmacokinetics are independent of dose over this dose range.

Liquid chromatographic assay of moxidectin in human plasma for application to pharmacokinetic studies.

A sensitive and selective high-performance liquid chromatography (HPLC) method is presented for the analysis of moxidectin in human plasma. Solid phase extraction using Oasis HLB cartridges is used for sample preparation. The fluorescent derivative is obtained by a dehydrative reaction with trifluoroacetic anhydride and N-methylimidazole. Separation is achieved on a Bondapak C(18) reversed-phase column with a mobile phase composed of tetrahydrafuran-acetonitrile-water (40:40:20, v/v/v). Detection is by fluorescence, with excitation at 365 nm and emission at 475 nm. The retention times of moxidectin and internal standard, ivermectin are approximately 10.7 and 18.6 min, respectively. The assay is linear over the concentration range 0.2-1000 ng/ml for moxidectin in human plasma (r=0.9999, weighted by 1/concentration). Recoveries at concentrations 0.2, 400, 1000 ng/ml are 94, 75, and 71%, respectively. The analysis of quality control (QC) samples for moxidectin (0.2, 400, and 1000 ng/ml) demonstrates excellent precision with relative standard deviations of 11.9, 5.7, and 2.7%, respectively (n=6). The method is accurate with all intra- (n=6) and inter-day (n=18) mean concentrations within (5.0%) from nominal at all QC sample concentrations. Moxidectin was found to be stable after three free-thaw cycles, and with storage at -20 and -80 degrees C for 12 weeks. The method is suitable for pharmacokinetic studies of moxidectin after oral administration to humans.