Apparent Clearance of Valproic Acid in Patients with Mania Associated with Bipolar Disorders in Sarawak General Hospital and Sentosa Hospital

Abstract

Introduction:

Valproic acid (VPA) is one of the medication options for patients with bipolar disorder. Dose initiation can be based on estimated patient clearance of 7-12ml/kg/hr. Patients with mania associated with bipolar disorder were found to have a higher clearance compared to patients with epilepsy, hence the estimated clearance may not be accurate in this patient population. This study aimed to investigate the population clearance value of valproic acid in patients with mania associated with bipolar disorder in Sarawak General Hospital (SGH) and Sentosa Hospital.

Methods:

This retrospective study entailed extraction of data from Therapeutic Drug Monitoring (TDM) request forms received from both hospitals in the year 2017. Included patients were stabilized for 3 months on VPA monotherapy for their mania, not on concurrent medication which can affect the clearance of VPA, no renal and hepatic impairments and claimed to be compliant. Clearance was calculated based on the formula Clearance (L/hr) = [VPA dose(mg)]/[Clearance at steady state (Css) measured (mcg/ml) x Interval (hr)]. Both salt factor and bioavailability were assumed to be 1.0 except for sustained release tablet which was 0.9. Clearance difference between gender was analysed using Independent t-test. Correlation was measured by Pearson correlation test to analyse the correlation between clearance and the age, weight and dose.

Results:

A total of 67 samples were taken. Mean age, weight and dose were 41.1 years (SD 14.86), 67.0kg (SD 16.10) and 1037mg (SD 395.75) respectively. The mean clearance (Cl/F) was found to be 9.20ml/kg/hr (SD 4.19). A negative but weak correlation (r=-0.29) was found between the weight (kg) and mean clearance (Cl/F) of patients (p=0.02).

Conclusion:

Localised population clearance values enable a more precise dose recommendation for patients on VPA therapy for mania associated with bipolar disorder. A statewide study on VPA pharmacokinetic profile in this patient population is recommended to be performed to further validate the clearance value, enabling optimal dosing of VPA during initiation of treatment.