Abstracts

Therapeutic monitoring (TM) of plasma valproate concentrations [VPA] is routine; the lowest concentration (trough) during a dosing interval is often used. While clinicians have experience using TM for conventional formulations, their TM experience with divalproex extended-release [ER], a novel formulation intended for once daily administration ([italic]Clin Drug Invest[/italic] 2003; 23: 661-70), may be limited. Questions have risen concerning the optimal time for obtaining a blood sample in relation to the dose, considering daily ER can be administered either in the morning or evening ([italic]Epilepsia[/italic] 2003; 44 [suppl 9]; 96). Predose or trough sampling is easily achieved just prior to morning daily dosing of ER, but the best time to sample after an evening daily dose is unclear. This investigation provides information and practical guidance regarding blood sample timing. Steady state [VPA]-time profiles from 5 published ER studies ([italic]Clin Drug Invest [/italic]2004, in press) in healthy subjects and epilepsy patients on enzyme-inducing antiepileptic drugs were analyzed. The [VPA] profile for each subject was expressed as a percentage of that subjects trough concentration and summary statistics computed. A pooled estimate of the standard deviation across time was computed. For the typical patient, plasma valproate concentrations are 35, 35, 27, 25, 18, 13 and 3 percent higher than trough (i.e., 24-hour) concentrations at 3, 6, 9, 12, 15, 18 and 21 hrs after the last ER once-daily dose, respectively. For the typical patient taking ER once-daily in the morning, e.g., 8 AM, blood samples collected 21 to 24 hrs after the last ER dose is expected to have concentrations within 3% of the trough value. Conversely, for the typical patient taking ER once-daily in the evening, e.g., 8 PM, collecting blood samples 21 to 24 hrs after the last ER dose may be limited by the operational hrs of the laboratory. For typical patients dosed in the evening, a blood draw 12 to 15 hrs after the dose (i.e., 8 to 11 AM) will give plasma valproate concentration values that are 18 to 25% higher than trough values. However, waiting longer, e.g., 18 to 21 hrs (i.e., 2 to 5 PM), will result in concentration values that are merely 3 to 13% higher than trough values. The pooled standard deviation around the reported percentage change for the typical patient was 26%. It should be recognized that because of intra and intersubject variability, individual patients might have wider range than the typical patient. The greatest deviation from the trough concentration occurs around Cmax, i.e., 3 to 9 hrs after a once-daily ER dose; sampling during this time period is not recommended. For patients taking daily ER in the evening, a blood sample obtained at least 18 hrs post-dose may be acceptable. (Supported by Abbott Labs)