[Treatment of Tritrichomonas foetus in a cat colony with delayed release ronidazole tablets in the small intestine]. / Behandlung einer an Tritrichomonas foetus erkrankten Katzen-Kolonie mittels Ronidazoltabletten unter verzögerter Wirkstofffreisetzung im Dünndarm.

Seven abyssinian cats (two male, five female) showed intermittent green-yellow mucous diarrhoea, sometimes an inflammation of the anal region and faecal incontinence even after long-time treatment with fenbendazole against Giardia. During necropsy of one of the cats, which had to be euthanized due to another disease, the gut wall of small and large intestine appeared macroscopically thickened. Histological examination indicated flagellates in the lumen of the intestine (initiating at the jejunum) and in the crypts. However Giardia could be excluded. in this case. By PCR of the faeces Tritrichomonas (T) foetus was diagnosed in five of six cats of this colony. Five remaining animals (another cat had to be euthanized) were treated with about 30 mg per kg BW ronidazole p. o. (rededication; Ridzol 10% Bt®, Dr. Hesse Tierpharma GmbH & Co. KG, Germany) daily over 14 days. The special gastro-resistant processing of the ronidazole should ensure a targeted effects. Animals were treated consecutively, isolated from the other cats and were daily examined clinically and neurologically. Neurotoxic adverse effects appeared slightly, therefore--as a precaution--the treatment of two cats was paused for one day. After treatment of all cats, T. foetus wasn't diagnosed by PCR over the period of 345 to > 800 days in any cat. One animal had dubious findings in the ninth week after treatment. Hence it was still kept isolated from the group and PCR showed a negative result at all times afterwards. The treatment protocol shows that elimination of problematic protozoal infections is possible in cat colonies.

Ronidazole pharmacokinetics in cats following delivery of a delayed-release guar gum formulation.

Ronidazole (RDZ) is the only known effective treatment for feline diarrhea caused by Tritrichomonas foetus. This study aimed to develop guar gum-coated colon-targeted tablets of RDZ and to determine the pharmacokinetics of this delayed-release formulation in cats. Guar gum-coated tablets were administered orally once to five healthy cats (mean dose 32.3 mg/kg). The tablets were then administered once daily for 5 days to four cats (mean dose 34.5 mg/kg), and absorption studies repeated on day 5. Plasma was collected and analyzed for RDZ concentration, and pharmacokinetic noncompartmental and deconvolution analysis were performed on the data. There was negligible RDZ release until after 6 h, and a delayed peak plasma concentration (mean Cmax 28.9 µg/mL) at approximately 14.5 h, which coincides with colonic arrival in cats. Maximum input rate (mg/kg per hour) occurred between 6 and 16 h. This delayed release of ronidazole from guar gum-coated tablets indicates that release of RDZ may be delayed to deliver the medication to a targeted area of the intestine. Repeated dosing with guar gum tablets to steady-state did not inhibit drug bioavailability or alter the pharmacokinetics. Such targeted RDZ drug delivery may provide improved efficacy and reduce adverse effects in cats.

Ronidazole pharmacokinetics after intravenous and oral immediate-release capsule administration in healthy cats.

Ronidazole (RDZ) is an effective treatment for feline Tritrichomonas foetus infection, but has produced neurotoxicity in some cats. An understanding of the disposition of RDZ in cats is needed in order to make precise dosing recommendations. Single-dose pharmacokinetics of intravenous (IV) RDZ and immediate-release RDZ capsules were evaluated. A single dose of IV RDZ (mean 9.2mg/kg) and a 95mg immediate-release RDZ capsule (mean 28.2mg/kg) were administered to six healthy cats in a randomized crossover design. Plasma samples were collected for 48 h and assayed for RDZ using high pressure liquid chromatography (HPLC). Systemic absorption of oral RDZ was rapid and complete, with detection in the plasma of all cats by 10 min after dosing and a bioavailability of 99.64 (±16.54)%. The clearance of RDZ following IV administration was 0.82 (±0.07) ml/kg/min. The terminal half-life was 9.80 (±0.35) and 10.50 (±0.82) h after IV and oral administration, respectively, with drug detectable in all cats 48h after both administrations. The high oral bioavailability of RDZ and slow elimination may predispose cats to neurotoxicity with twice-daily administration. Less frequent administration should be considered for further study of effective treatment of T foetus-infected cats.

Plasma ronidazole concentrations in sheep after intravenous, oral, intraruminal and intraabomasal administration.

Plasma ronidazole concentrations were examined after intravenous (i.v.) and oral administration of ronidazole in sheep (n = 6) at a dosage of 5 mg/kg body weight. In three sheep a ruminal and an abomasal fistula were inserted. The ronidazole determinations were performed by an HPLC method. Oral bioavailability in the fistulated sheep was only 5.5 +/- 1.8% (mean +/- SE). Somewhat lower values (4.6 +/- 1.4%) were obtained when the drug was administered through the ruminal fistula in the rumen. After administration of the same dose directly in the abomasum through the intraabomasal fistula, bioavailability was increased to 86.0 +/- 8.9%. In the non-fistulated sheep, oral biodisponibility was 2.6 +/- 0.5%. After water was restricted for 48 h before the oral ronidazole administration to these sheep, bioavailability was slightly increased (6.0 +/- 3.1%). When desmopressin acetate was injected i.v. before the oral ronidazole administration, bioavailability was 10.6 +/- 6.5%. When glypressin, another vasopressin analogue, was used, oral bioavailability was not influenced: 2.4 +/- 1.3%. Ronidazole was also incubated with ruminal contents and the ronidazole concentration decreased with a first order rate constant of 0.122 +/- 0.050 min-1 (mean +/- SE). These results suggest that oral administration of ronidazole to sheep is of little therapeutic use, because most is metabolised by the ruminal micro-organisms before it can reach the circulation. A second conclusion we can make is that it is very difficult, if not impossible, at least with the methods used, to influence gastro-intestinal motility in sheep to get a reproducible closure of the oesophageal groove.

Influence of feeding on the bioavailability of ronidazole prolonged-release formulations in pigeons.

The influence of feeding on the bioavailability of ronidazole (5 mg per animal) formulated as a hydrophilic-matrix tablet or as lipophilic pellets, was evaluated in pigeons. Administered to fed pigeons, prolonged drug absorption was obtained for both formulations. In non-fed pigeons an immediate grinding of the formulations in the gizzard resulted in rapid drug absorption. This indicates that prolonged residence of the prolonged-release formulations in the crop obtained in the fed condition seemed the only possible means of obtaining prolonged drug release in pigeons.

Pharmacokinetics and bioavailability of ronidazole from a prolonged release tablet in the homing pigeon (Columba livia).

The pharmacokinetics of ronidazole and the bioavailability of a prolonged release tablet were studied in the homing pigeon. After intravenous administration of 5 mg ronidazole, the drug plasma concentration profile fitted a one-compartment open model. The mean half-life of the drug was 11 h and the volume of distribution was 0.86 l/kg. Total body clearance was 0.056 l/h/kg. A sustained release matrix tablet exhibited prolonged drug release in vitro. After oral administration of the matrix tablet to pigeons drug absorption was nearly complete. When given on an empty stomach, the tablet failed as a prolonged release system. Administration to previously fed pigeons resulted in an increase in tmax and a decrease in Cpmax.