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

Abstract

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 diet on the pattern of gastrointestinal biotransformation of netobimin and albendazole sulphoxide in sheep

“…The rumen bacteria are capable of either activating or de-activating drugs and toxic compounds. For instance, ruminal biodegradation of active drugs such as the antiprotozoan compound ronidazole (2) ig. I: Proposed metabolic pathway for netobimin (NTB) pro-drug and its metabolites: albendazole (ABZ) and albendazole sulphoxide (ABZSO).…”

Moxidectin and ivermectin metabolic stability in sheep ruminal and abomasal contents

“…Although the liver is the main site for the biotransformation of xenobiotic compounds, drug metabolism also takes place in extra‐hepatic tissues such as the gastrointestinal tract, which may contribute to reduce the systemic availability of orally administered compounds (Rowland, 1986; Vynckier & Debackere, 1993). The anthelmintics netobimin (an albendazole prodrug) and ABZSO have been shown to suffer extensive biotransformation in ruminal (Virkel et al.…”

“…A low amount of [ 3 H]-doramectin in abomasal digesta was collected in sheep after its intravenous administration, that reflect the minimal gastric secretions of ML (Hennessy et al, 2000). Although the liver is the main site for the biotransformation of xenobiotic compounds, drug metabolism also takes place in extra-hepatic tissues such as the gastrointestinal tract, which may contribute to reduce the systemic availability of orally administered compounds (Rowland, 1986;Vynckier & Debackere, 1993). The anthelmintics netobimin (an albendazole prodrug) and ABZSO have been shown to suffer extensive biotransformation in ruminal and intestinal (Lanusse et al, 1992) contents collected from sheep and cattle.…”

Influence of ruminal distribution on norfloxacin pharmacokinetics in adult sheep

“…This suggest that the low p.o. bioavailability registered in sheep is not related to NF formulation but it could be attributed to incomplete absorption, first‐pass metabolism in the liver or rumen or, more likely, binding of the drug to food particles (Vynckier & Debackere, 1993). Ruminal biodegradation of fluoroquinolones is a likely explanation for low bioavailability but, in our study, NF ruminal concentration–time curves after p.o.…”