The effect of Valproic acid - Carbapenem antibiotics Interaction on Pharmacokinetics of Valproic acid and Seizure Development

Background: Valproic acid is widely used in the treatment of generalized tonic-clonic and partial seizures. The carbapenem class is the most potent and widest spectrum of antimicrobial activity. Concomitant administration of carbapenems and valproic acid has been reported to decrease the serum concentration of valproic acid, which is sometimes associated with seizures. The purpose of this study is to evaluate the changes in valproic acid concentration and half life and the frequency of seizure during concomitant administration of valproic acid and carbapenems. Method: This study was performed retrospectively on total 40 cases with identified valproic acid concentration during concomitant administration of valproic acid and carbapenems at Kangbuk Samsung Hospital from February 1st, 2006 to October 31st, 2011. Patients were classified into 3 groups: ertapenem group (n=14), imipenem group (n=12), meropenem group (n=14). Results: The mean serum concentrations in each group during combined treatment were $9.50{\pm}8.84$, $21.88{\pm}8.17$ and $10.62{\pm}8.67$ mg/L, respectively (p < 0.001). The mean half-lives in each group during concurrent use of valproic acid and carbapenems were $3.18{\pm}0.81$, $4.63{\pm}1.97$ and $2.67{\pm}1.69$ hr, respectively (p < 0.001). The valproic acid serum concentration decreased by 75.5%, 54.1% and 84.1% and the half-life of valporoic acid decreased by 65.6%, 35.7% and 73.5%, respectively. Total cases with seizure were 12(30%) with 5(35.7%) in the ertapenem group, 3 (25.0%) in the imipenem group and 4(28.6%) in the meropenem group (p=0.911). There were no specific factors to influence on seizure development during combined treatment. Conclusion: Concurrent use of carbapenems and valproic acid should be avoided. If concomitant administration is essential, very close serum concentration monitoring and clinical observation are necessary.

Valproic acid와 Carbapenem계 항생제 병용 투여로 인한 Valproic acid의 약동학적 변화 및 경련 발생에 대한 고찰