The influence of the rumen on the absorption of drugs: studies using meclofenamic acid administered by various routes to sheep and cattle

Abstract

As part of a general study of the pharmacokinetics of drugs in the ruminant animal, the absorption and distribution kinetics of meclofenamic acid between the gastro‐intestinal tract and plasma of sheep and cattle were investigated. Meclofenamic acid is a non‐steroidal anti‐inflammatory drug which has been shown to possess anti‐anaphylactic activity in cattle (Aitken & Sanford, 1969; 1972; Wells, Eyre & Lumsden, 1973) and sheep (Alexander, Eyre, Head & Sanford, 1970) and although marketed only for the horse in the United Kingdom (Arquel, Warner‐Lambert) is known to be used in ruminant animals as an anti‐inflammatory drug, for its inhibitory effects on prostaglandin synthesis (Smith G. G. A. 1977, personal communication) and for its anti‐pyretic action (Van Miert, Van der Wal‐Komproe & Van Duin, 1977). The aims of the study were first to evaluate the contribution of reticular (oesophageal) groove closure in directing orally administered drug directly to the abomasum and to assess the rate of absorption through the ruminal epithelium. Second, since Aitken & Sanford (1975) have described the plasma levels of meclofenamate after administration of sodium meclofenamate to cattle by the oral, intravenous and intra‐ruminal routes, it was decided to complement their study and to measure the plasma levels after intra‐muscular injection of sodium meclofenamate. This route is more convenient in cattle than the oral and intravenous routes examined by them. Lastly, the biphasic pattern of plasma levels of meclofenamate observed by Aitken & Sanford (1975) following oral administration of sodium meclofenamate to cattle was further examined using weaned and unweaned calves in an attempt to confirm their view that some of the drug is delivered to the abomasum directly, by‐passing the rumen, by closure of the reticular groove.

Pharmacokinetics of oral meloxicam in ruminant and preruminant calves

“…This increased variability within the preruminant groups may have been because of a combination of factors such as amount of starter ration and/or milk replacer consumed on the day of dosing, the presence of undiagnosed enteric pathology, differences in maturation of the hepatic metabolic enzyme system, differences in rumen maturity, and closure kinetics of the reticular groove while consuming the dose in milk replacer. (De Backer & Debackere, 1979; Marriner, 1979; Nouws,1992).…”

Comparison of the Kinetics of Sodium Meclofenamate Versus Meclofenamic Acid after Oral Administration to Sheep

“…In previous works, it has been shown that the reticular groove closure could modify the kinetic disposition of drugs including meclofenamates (MARRINER and BOGAN, 1979;ENCINAS, 1993). Therefore, whenever drugs are administered by the oral route to ruminants, the effect of reticular groove closure must be considered (SUITER et al, 1993).…”

“…In cattle, studies with meclofenamates after intravenous, oral, intraruminal (AITKEN and SANFORD, 1975) and intramuscular administration (MARRINER and BOGAN, 1979) were reported. In sheep, however, there are only published works with sodium meclofenamate administered by the oral and intramuscular routes (MARRINER and BOGAN, 1979). In their study, a biphasic absorptive pattern was described, which could be due to some of the drug by-passing the rumen, through the reticular groove.…”

High performance liquid chromatography and pharmacokinetics of the non‐steroidal anti‐inflammatory drug oxindanac in calves

“…administration to cattle (Aitken & Sanford, 1975) and sheep (Marriner & Bogan, 1979) were attributed to closure of the oesophageal groove, allowing some of the drug to enter directly into the abomasum while the rest was retained, temporally, in the rumen. The rate of absorption of acidic NSAIDs such as meclofenamate and oxindanac should be considerably faster from the acidic environment of the abomasum rather than from the rumen (Marriner & Bogan, 1979). This mechanism could have operated in this study as the calves were only 4-6 weeks of age and consumed both milk and roughage.…”