Development of mechanisms for drug excretion

Abstract

Renal excretion of many drugs is less in the newborn than what would be predicted in terms of body weight. This is due, in part, to low renal blood flow and glomerular filtration rate during the immediate newborn period. In the first weeks to months of postnatal life, renal vascular resistance decreases and blood flow increases. Subsequently, the glomerular filtration rate increases. During this time, drug elimination may also be affected by qualitative and quantitative differences in binding of drugs to plasma proteins. In addition, drug elimination may be prolonged due to an immature ability in the newborn to transport or metabolize drugs in the kidney. Recent evidence demonstrated that drugs administered pre- or postnatally may alter the rate of renal excretion of drugs in the newborn. Such effects are of great concern to the clinician and underscore the importance of monitoring drug blood levels in these patients. From another perspective, the ability to stimulate drug excretion has been used as a tool to study basic renal physiology. Quantitative patterns of development coupled with the use of substrate stimulation provided evidence for at least three transport systems for organic anions in the proximal tubule. Similar technics provided preliminary data linking drug metabolism and organic anion transport in the proximal tubule, whereas an obligatory, rate-limiting role for ligandin in anion transport could not be established.