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Pharmacokinetics of the antimicrobial drug Sulfanilamide is altered in a preclinical model of vascular calcification

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In vascular smooth muscle, calcium overload is linked to advancing age. The pharmacokinetics of Sulfanilamide (SA), a compound with antibacterial properties, was evaluated in a preclinical model of vascular calcification. SA was used since it is useful to study possible modifications in the renal and hepatic management of drugs. Vascular calcification was induced by administration of a single high dose of vitamin D3 to rats (treated group) 10 days before the experiments. A parallel control group was processed. The decrease of renal blood flow due to calcification of the renal arteries explains, at least in part, the decrease in the renal clearance of SA observed in treated rats. The liver metabolic function increased in treated rats as demonstrated by increases in plasma appearance rate of acetylated‐Sulfanilamide (ASA), hepatic ASA content and hepatic N‐acetyltransferase activity. The decrease in renal excretion of SA was not completely compensated by the hepatic metabolism increase, since the elimination rate of SA from the central compartment (K1‐0) decreased in the treated group. In summary, in this experimental model with sustained arterial calcinosis induced by a single high dose of vitamin D3 10 days before the experiments, the pharmacokinetics of an aminobenzenesulfonamide is modified, at least in part, by the increase in the activity of hepatic N‐acetyltransferase and the decrease in renal blood flow. This study emphasizes the importance of considering the presence of vascular calcification when a drug dose scheme is performed, in order to optimize pharmacotherapeutic results.
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Keywords: N‐acetyltransferase; arterial pressure; calcium; hepatic function; pharmacokinetics; renal function; sulfonamides; vascular calcification; vitamin D3

Document Type: Research Article

Publication date: December 1, 2017

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