Interaction of host physiology and efficacy of antiparasitic drugs

Antiparasitic drugs must be conducted to the parasite by the host and are therefore subject to physiological and biochemical processes in the host. Usually the efficacy of an antiparasitic drug will depend on a toxic concentration being presented to the parasite for sufficient time to lead to irreversible damage. Because many drugs are, in part, absorbed and transported to the site of the parasite by the circulatory system the area under the plasma concentration curve (AUC) may reflect availability of drug to the parasite and likely efficacy. A number of host physiological factors affect the AUC. Many anthelmintics are given orally as solids. Some absorption occurs in the rumen of ruminants, but many heterocyclic compounds such as the benzimidazoles require the low pH of the abomasum or gastric stomach to render them soluble. Certain disease states, including gastrointestinal parasitism, can cause the gastric pH to rise. This may in turn reduce solubility and absorption with resultant faster rate of excretion, particularly when accompanied by diarrhoea, and a reduced AUC. Once the anthelmintic has been absorbed, after oral or systemic administration, it is usually rapidly transported to the liver. The liver and adipose tissue may store the drug, releasing it over a period to produce a sustained effect as occurs with ivermectin, or it may rapidly metabolise it. A few anthelmintics, such as febantel, probably need to be metabolised in order to become active. However, more frequently the liver is involved in oxidation or reduction, followed by conjugation with sulfate, glucuronide or glutathione to render the drug more polar, to increase its molecular weight, inactivate it and facilitate its excretion. The rate of metabolism has been found to vary considerably between species and thus different dose rates and treatment are often required to achieve adequate antiparasite activity, with species such as deer, cattle and probably goats metabolising some anthelmintics faster than sheep. Some interesting possibilities for altering the absorption and metabolism of anthelmintics by the host may allow improved efficacy and reliability of antiparasite activity without necessarily increasing the dose rate of anthelmintic.