Drug metabolism reviews
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Drug metabolism reviews · Jan 2007
ReviewInteraction between valproic acid and carbapenem antibiotics.
The serum concentration of valproic acid (VPA) in epilepsy patients decreased by the administration of carbapenem antibiotics, such as meropenem, panipenem or imipenem, to a sub-therapeutic level. This review summarized several case reports of this interaction between VPA (1-4 g dose) and carbapenem antibiotics to elucidate the possible mechanisms decreasing VPA concentration by carbapenem antibiotics. Studies to explain the decrease were carried out using rats by the following sites: absorption of VPA in the intestine, glucuronidation in the liver, disposition in blood and renal excretion. ⋯ Plasma VPA distributed to erythrocytes by the inhibition of transporters (Mrp4), which efflux VPA from erythrocytes to plasma, by carbapenem antibiotics. The increase of renal excretion of VPA as VPA-Glu depends on the increase of VPA-Glu level by UGT. One or a combination of some factors in these mechanisms might relate to the carbapenem-mediated decrease of the plasma VPA level.