4.3 Article

Pharmacokinetics of organic anions in rats with arterial calcinosis

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WILEY
DOI: 10.1046/j.1440-1681.2002.03604.x

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arterial calcinosis; organic anions; pharmacokinetics; systemic clearance; vitamin D3

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1. Ageing induces calcium accumulation in the vascular system. The simplest experimental way of producing high degrees of arterial calcium overload is by admininistration of an overdose of vitamin D-3 to rats. The aim of the present study was to evaluate the pharmacokinetics of organic anions in rats with arterial calcinosis induced by an overdose of vitamin D-3. 2. We used bromosulfophthalein (BSP) and sulfanilamide (SA) as models of organic anions with preferential biliary and renal excretion, respectively. 3. Increases in the clearance and elimination rate constant of BSP were observed in treated rats. The clearance and the elimination rate constant for SA were also increased in rats with arterial calcinosis. 4. Variations in arterial hepatic blood flow, aspartate aminotransferase activity and liver calcium accumulation were not observed in treated rats. In contrast, treated rats had a lower renal blood flow and increased renal calcium levels. 5. In summary, rats with arterial calcinosis showed an increase in total body clearance of both BSP and SA, probably associated with modifications in their metabolism and/or in organ extraction. Alterations to hepatic and renal blood flow do not account for these phenomena.

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