Grundlegende Studien mit Petasites hybridus Extrakt Ze 339 bei Pferden: Pharmakokinetik und Bioverfügbarkeit bei klinisch gesunden Pferden sowie Wirkstudien bei Pferden mit Recurrent Airway Obstruction.
Pilot studies with Petasites hybridus extract Ze 339 with horses: Pharmacokinetics and bioavailability in healthy horses and efficacy studies with horses suffering Recurrent Airway Obstruction
Dissertation, Vet. Med. Univ. Wien, pp. 81.
The aim of the presented study was to investigate the pharmacokinetic of the P. hybridus extract Ze 339 and test for treatment efficacy and tolerance on horses suffering Recurrent Airway Obstruction (RAO). Since years the extract is a well accepted medicine for humans against allergic rhinitis, headache, cough, spasm of the gastrointestinal tract as well as the urogenital tract. The positive effect is due to the inhibition of mastcell degranulation, the reduction of smooth muscle spasm, the anti-inflammatory effect as well as the inhibition of leukotriene biosynthesis. The extract contains many of the desired properties for the treatment of horses suffering RAO. This disease is dominated by inflammatory reactions in the airways, hyperresponsiveness, bronchoconstriction and mucus accumulation. The application of Ze 339 in horse was never proofed scientifically in horses. The first phase of the study was to establish a sensitive LC/MS/MS method for plasma and urine samples. The active compounds petasin, neo- and isopetasin had a limit of detection of 5 ng/ml. The pharmacokinetic study showed that horses are able to absorb the extract, which was administered via nasogastric-tube (10 to 40 mg/kg bm dry extract). The plasma level presented a Cmax from 19 to 673 pg/ml. This suggested poor bioavailability, implicating that oral application would be a poor route of administration. Therefore the next step of the study was to develop a solution for inhalation. This new solution was tested for preliminary safety, tolerance, and efficacy on horses suffering RAO. All horses could finish the studies and no negative side effects were detected during the one dose inhalation therapy with the new solution. The lung function tests (FOM, methacholine challenge, ΔPpl measurements, BALF analyses and Interleukin 8 measurements) could prove that there was a drug-induced bronchospasm. Measurements at low oscillation (2 Hz) suggested decrease of bronchoconstriction. After one week of treatment a significant improvement at 2 Hz showed a bronchodilatory effect. These first observations showed the therapeutic potency of P. hybridus for horses suffering RAO. This observation was further supported by the inhibition of IL-8 release seen in BALF samples after treatment. The last phase of the project was an observational qualitative field study. The oral therapy was tested for apparent efficacy. The evaluations of treatment effect were performed by treating veterinarians who filled in questionnaires as well as by the owners or riders of the horses. First results could indicate that the extract is well tolerated during the whole treatment period and RAO signs ameliorated.