Abnormal reduction of valproic acid plasma concentration caused by carbapenem antibiotics

QI Yang; ZHOU Yu; SONG Hongtao

doi:10.3969/j.issn.1006-0111.2018.04.019

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Objective To discuss the risk factors affecting the metabolism of valproic acid (VPA),improve the rational medication and reduce the rate of epilepsy recurrence. Methods Two hospitalized patients were analyzed after being administrated VPA for epilepsy prevention or treatment,with serum VPA levels less than 1 μg/ml. The relevant reasons in literature review in many aspects were collected by clinical pharmacists,such as drugs interaction,hepatic drug-metabolizing cytochrome P450 (CYP) enzymes activity and genetic polymorphism. Results The reduced serum VPA levels were primarily caused by combination of valproic acid and carbapenem. The co-administration of Phenobarbital and rifamycin sodium,as CYP inducers,promoted the metabolism of valproic acid. In addition,the two patients carried mutant allele of CYP2C19,with middle or low grade of VPA metabolism ability. These indicated the dominant role of the medication interaction and the enhanced CYP450 activity in leading to the reduced VPA serum levels. Conclusion Clinicians should closely monitor the serum VPA concentration and the recurrence of seizures when carbapenem and VPA combined.

Abnormal reduction of valproic acid plasma concentration caused by carbapenem antibiotics

Department of Pharmacy, Fuzhou General Hospital, Fuzhou 350025, China

Received Date: 2017-08-25

Rev Recd Date: 2018-01-04

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Abstract: Objective To discuss the risk factors affecting the metabolism of valproic acid (VPA),improve the rational medication and reduce the rate of epilepsy recurrence. Methods Two hospitalized patients were analyzed after being administrated VPA for epilepsy prevention or treatment,with serum VPA levels less than 1 μg/ml. The relevant reasons in literature review in many aspects were collected by clinical pharmacists,such as drugs interaction,hepatic drug-metabolizing cytochrome P450 (CYP) enzymes activity and genetic polymorphism. Results The reduced serum VPA levels were primarily caused by combination of valproic acid and carbapenem. The co-administration of Phenobarbital and rifamycin sodium,as CYP inducers,promoted the metabolism of valproic acid. In addition,the two patients carried mutant allele of CYP2C19,with middle or low grade of VPA metabolism ability. These indicated the dominant role of the medication interaction and the enhanced CYP450 activity in leading to the reduced VPA serum levels. Conclusion Clinicians should closely monitor the serum VPA concentration and the recurrence of seizures when carbapenem and VPA combined.

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Reference (15)

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Abnormal reduction of valproic acid plasma concentration caused by carbapenem antibiotics

doi: 10.3969/j.issn.1006-0111.2018.04.019

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通讯作者: 陈斌, [email protected]

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