Excretion of organic acids and bases was studied in twelve fetal sheep aged 120-140 days. There was no significant plasma protein binding of the organic anion, p-aminohippurate (PAH), nor of the organic cation, [14C]tetraethylammonium (TEA). There was a significant amount of acetyl-PAH (20 +/- 3%) in fetal urine but none could be detected in fetal plasma. The fractional excretion of unconjugated PAH was less than one, i.e. there was net reabsorption of 31.7 +/- 3.9% of the filtered load of unconjugated PAH. Since there was no acetyl-PAH in fetal plasma it is concluded that all acetyl-PAH in fetal urine occurred as a result of metabolism of PAH and secretion of the metabolite into the tubular lumen. The rate of excretion of acetyl-PAH in fetal urine varied from 0 to 14.0 micrograms min-1. Thus unconjugated PAH is filtered and there is net reabsorption; in addition, PAH is metabolized and enters the urine via tubular mechanisms. The fractional excretion of PAH was unaffected by I.V. administration of penicillin either acutely or chronically. The clearance of [14C]TEA was significantly greater than the glomerular filtration rate (GFR). The mean fractional excretion of [14C]TEA was 5.4 +/- 0.17. Thus 80.7 +/- 0.63% of the excreted TEA was secreted. The clearance of TEA was related to body weight (P less than 0.001) but the fractional excretion of TEA declined with gestation age, probably because GFR increased at a greater rate than the rate at which the secretory pathways increase their activity. It is concluded that those pathways that excrete organic anions like PAH into the urine mature much later (probably after birth) than those pathways responsible for the tubular secretion of organic bases.

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