Canine CYP2B11 metabolizes and is inhibited by anesthetic agents often co-administered in dogs.

Medetomidine is a well-established sedative and analgesic for dogs and cats. As a premedicant for anesthesia regimens that also include other agents, medetomidine can also provide a dose-sparing effect. While there are likely several reasons for the dose-sparing effect of medetomidine, the role of metabolic drug-drug interactions at the single enzyme level has not yet been examined. Using a panel of individually expressed canine cytochromes P450 cloned from beagle liver, this report demonstrates that medetomidine is an extremely potent CYP2B11 inhibitor (IC(50) < 10 nm) and that ketamine and midazolam are CYP2B11 substrates with high intrinsic clearances. These in vitro findings suggest that under some circumstances, medetomidine (i.e. 'perpetrator') may inhibit the metabolic clearance of some high metabolic clearance drugs (i.e. 'victims') with which it is commonly co-administered via the CYP2B11 pathway. However, as the dose-sparing effect of medetomidine premedication commonly results in anesthetic dose reduction, any increased plasma concentrations of victim drugs caused by medetomidine would still be lower than if no dose reduction had been made. Further studies are needed to characterize whether medetomidine possesses the potential to cause pharmacokinetic interactions. In conclusion, the ability of recombinant P450s to define canine-specific drug clearance pathways and P450 inhibitors should prove useful in identifying drug combinations that may require dose adjustments in dogs.

Antioxidant and antimicrobial activity of Foeniculum vulgare and Crithmum maritimum essential oils.

The essential oils obtained from Crithmum maritimum L. (marine fennel) and two samples of Foeniculum vulgare Miller (common fennel) were analysed by GC and GC-MS and assayed for their antioxidant and antibacterial activities. The antioxidant activity of the oils was evaluated by two lipid model systems: a modified thiobarbituric acid reactive species (TBARS) assay and a spectrophotometric detection of hydroperoxydienes from linoleic acid in a micellar system. The oils demonstrated antioxidant capacities, comparable in some cases to that of alpha-tocopherol and butylated hydroxytoluene (BHT), used as reference antioxidants. Concerning the antimicrobial tests the essential oils were assayed against twenty-five genera of bacteria, including animal and plant pathogens, food poisoning and spoilage bacteria. Oils from the two samples of F. vulgare showed a higher and broader degree of inhibition than that of C. maritimum.

Plasma protein binding of celecoxib in mice, rat, rabbit, dog and human.

The plasma protein binding of celecoxib was determined for animals and humans using in vitro and ex vivo methods. Eight, healthy, human volunteers (three male, five female, 20-39 years) received celecoxib (600 mg) BID for 7 days, blood samples were collected and concentrations of bound and unbound celecoxib determined. The fraction of bound drug in the volunteers was constant (97.4 +/- 0.1%) at total celecoxib plasma concentrations ranging from 0.01 to 4.02 microg/mL. The ex vivo plasma protein binding of celecoxib in the animals was concentration-independent up to approximately 12, 8 and 10 microg/mL for mouse, rat and dog, respectively. The plasma protein binding of celecoxib after a single oral dose of 10 and 300 mg/kg to mice was 98.3 +/- 0.2%, of 1 and 400 mg/kg to rats was 98.3 +/- 0.2% and of 1 and 100 mg/kg to dogs was 98.5 +/- 0.1%. The percent binding of celecoxib to plasma proteins in vitro was slightly lower than those values determined ex vivo. The in vitro binding of celecoxib to plasma protein was constant over the concentrations of 0.1-10 microg/mL for all species, except rat.

Cycloartane triterpene glycosides from Astragalus siculus.

Based on spectroscopic analysis and chemical degradation, the structures of two saponins isolated from the methanol extract of fresh roots of Astragalus siculus Biv. were established to be that of astrasieversianin II and astragaloside I (also known as astrasieversianin IV), two saponins previously isolated from A. sieversianus Pall and A. membranaceus Benge. A complete assignment of NMR data to the two compounds is reported for the first time.