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Título del libro: Liver Pathophysiology: Therapies And Antioxidants
Título del capítulo: Drug Hepatic Clearance in Spinal Cord Injury

Autores UNAM:
PATRICIA GARCIA LOPEZ; LETICIA CRUZ ANTONIO; GABRIEL GUIZAR SAHAGUN;
Autores externos:

Idioma:
Inglés
Año de publicación:
2017
Palabras clave:

Naproxen; Paraplegia; Pharmacokinetic alteration; Phenacetin; Spinal cord injury (SCI); Sprague Dawly rat


Resumen:

There is evidence suggesting that spinal cord injury (SCI) may induce pharmacokinetic alterations; in particular, changes in drug metabolic clearance. We have therefore launched a research line on the characterization of drug disposition of test drugs eliminated mainly by hepatic clearance. Thus, we have characterized the pharmacokinetics of phenacetin and naproxen in experimental SCI. Phenacetin is submitted to high-hepatic extraction and hence its clearance depends on liver blood flow. Naproxen is a low-extraction drug and thus its clearance depends on enzyme activity in liver cells. In animals with SCI, clearance of phenacetin, but not of naproxen, was significantly impaired. We have also observed that SCI significantly impairs liver blood flow but does not produce any significant alteration in biochemical indicators of liver function. Our observations suggest that SCI induces hemodynamic changes resulting in a reduction in liver blood flow, but has no significant effect on intrinsic liver function. Such alterations affect the metabolic clearance of high-extraction drugs, but not of low-extraction drugs. © 2017 Elsevier Inc. All rights reserved.


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