The impact of ibuprofen on valproic acid plasma concentration in pediatric patients

Abstract

1. The combination of valproic acid (VPA) and ibuprofen are common in children with epilepsy. Three case reports investigated that ibuprofen might decrease the plasma concentration of VPA, however, no cohort study was published to evaluate the interaction of ibuprofen on VPA plasma concentration in pediatric patients.

2. Data from patients with measured VPA trough concentrations (C₀) were retrospectively collected in a Chinese teaching and tertiary Children’s Hospital from January 2017 to June 2019. The samples measured within 6 weeks of the last ibuprofen administration were considered ibuprofen combination samples. Patients with paired samples before and after ibuprofen administration were additionally analysed. The effects of ibuprofen on the VPA through concentration to dose (C₀/D) ratio were investigated. The proportion of samples with achieved target concentrations of VPA (50–100 mg/L) and the corresponding required dosage were compared. Moreover, subgroup analysis according to the interval between the last ibuprofen dosage and C₀ measurement was performed.

3. A total of 616 samples from 434 patients, of whom 16 had paired samples, were included. VPA C₀/D decreased when ibuprofen was administered by 7.5% and 30.6% of the total samples and paired samples, respectively. The interaction was significant within 1 week of the last ibuprofen dose. No significant differences were observed in the proportion of target concentration achieved and VPA dose requirement when ibuprofen was combined.

4. A moderate effect of ibuprofen on VPA C₀/D was observed within 1 week of ibuprofen administration; the target concentration and required doses of VPA were comparable.

Keywords:

• Ibuprofen
• valproic acid
• drug-drug interaction
• trough concentration
• pharmacokinetics

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81973396), Natural Science Foundation of Zhejiang Province (LSY19H300001), and Zhejiang Provincial Program for 151 Talents (to FL).