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.