Pharmacokinetics of cefovecin in cats.

The pharmacokinetics of the novel cephalosporin cefovecin were investigated in a series of in vivo, ex vivo and in vitro studies following administration to adult cats at 8 mg/kg bodyweight. Bioavailability and pharmacokinetic parameters were determined in a cross-over study after intravenous (i.v.

Pharmacokinetics and pharmacodynamics of cefovecin in dogs.

A series of in vivo, ex vivo and in vitro studies were conducted to determine the pharmacokinetic and pharmacodynamic properties of cefovecin, a new injectable cephalosporin, in dogs. Absolute bioavailability was determined in a two-phase cross-over study in dogs receiving 8 mg/kg bodyweight (b.w.

Selamectin is a potent substrate and inhibitor of human and canine P-glycoprotein.

The transport of the antiparasitic agents, ivermectin, selamectin and moxidectin was studied in human intestinal epithelial cell monolayers (Caco-2) and canine peripheral blood lymphocytes (PBL). Both models expressed the mdr1-coded 170 kDa ATP-binding cassette (ABC) transporter P-glycoprotein (P-gp). Fluxes of the P-gp substrate rhodamine-123 (Rh-123) across Caco-2 monolayers showed that ivermectin and selamectin acted as potent P-gp inhibitors with IC50 values of 0.

Disposition of 3H-selamectin and 3H-ivermectin in the brain of the cat flea Ctenocephalides felis felis using micro-image analysis.

In addition to intrinsic potency and metabolic stability, the disposition of an antiparasitic drug within the target parasite plays a major role in determining drug activity. A novel technique that allows the disposition of radiolabelled drugs to be visualised within the body of the cat flea (Ctenocephalides felis felis) is described. The concentrations of two macrocyclic lactones, (3)H-selamectin and (3)H-ivermectin, within the supra- and sub-oesophageal ganglia of the flea brain following in vitro feeding of fleas on different doses of drug solubilised in calf blood have been measured.

Novel anthelmintic metabolites from an Aspergillus species; the aspergillimides.

Two members of a novel class of anthelmintics, the aspergillimides, have been isolated from the Aspergillus strain IMI 337664. This novel fungus also produced two known and one structurally novel paraherquamide. This paper describes the fermentation, isolation, structure elucidation and anthelmintic activity of aspergillimide (VM55598, 1), 16-keto aspergillimide (SB202327, 2), and the paraherquamides VM54159 (3), SB203105 (4) and SB200437 (5).

Further novel milbemycin antibiotics from Streptomyces sp. E225. Fermentation, isolation and structure elucidation.

Ten novel alpha and beta class milbemycins have been isolated and characterized from the Streptomyces sp. E225, which has previously been shown to produce four related milbemycins. Some of the metabolites contain new structural features including, VM48641 which possesses an alpha-methoxyl substituent at C-27, and VM48642 which contains a furan ring at the terminus of the C-26 side chain.

Further novel metabolites of the paraherquamide family.

Four novel metabolites of a Penicillium strain, IMI 332995, which has previously been reported to produce paraherquamide and a number of related metabolites, are herein described. VM55596 is the first N-oxide to be found in this family of compounds. Unusual oxidative substitution is also seen in VM55597.

Reproducible pneumonia in gnotobiotic piglets induced with broth cultures of Mycoplasma hyopneumoniae and the effect of animal passage on virulence.

The virulence of a laboratory adapted culture of Mycoplasma hyopneumoniae strain NB12 was determined in three- to five-day-old gnotobiotic piglets. Intranasal inoculation or exposure to an aerosol of the culture caused low incidences of pneumonia in the piglets. Passage of M hyopneumoniae strain NB12 in gnotobiotic piglets resulted in a rapid increase in virulence.