Drug disposition in the neonatal animal, with particular reference to the foal

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Summary

Differences between neonatal and adult animals in their response to drugs can usually be attributed to altered disposition (ie, distribution, metabolism and excretion) processes during the neonatal period. These alterations affect the plasma concentrations as well as the concentrations of drug attained at the receptor site. Some characteristics of the neonatal period include greater absorption from the gastrointestinal tract, lower extent of plasma protein binding, increased apparent volume of distribution of drugs that distribute in extracellular fluid or total body water, increased permeability of the ‘blood-brain’ barrier and slower elimination of many drugs. The hepatic microsomal oxidative reactions and glucuronide conjugation are deficient metabolic pathways for a varying period of time, usually up to six weeks after birth or even longer in some species. Decreased metabolism can affect the duration of action of lipid-soluble drugs. Functional immaturity of the kidneys decreases the renal excretion of polar drugs and drug metabolites. Overall renal function appears to reach maturity within two weeks after birth in ruminant species and pigs, while maturation may take at least four weeks in other species of domestic animals. Considerable physiological and biochemical development takes place during the first five days after birth with maturation continuing more slowly over the succeeding five weeks. The time it takes for any process to reach functional maturity depends on the process in question and varies with the species of animal. The absorption, disposition and pharmacological response to drugs during the first 24 h after birth may be unique to that time and, because of lack of information, are impossible to predict.

The meagre evidence available suggests that processes responsible for metabolism and excretion of drugs develop comparatively rapidly in the foal. At present, however, there are no definitive pharmacokinetic or metabolic studies in the literature which can lead to firm recommendations on dosage regimens or serve as a basis for predicting the clinical pharmacokinetics of drugs during the neonatal period in the horse. However, there has been a recent surge of interest in drug dosage in foals and this review of the available literature and presentation of concepts may serve as a useful guideline.

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