title: Does it really matter when a blood sample for valproic acid concentration is taken following once-daily administration of divalproex-ER?
abstract: Divalproex sodium extended-release (divalproex-ER) is a novel formulation intended for once-daily oral administration, either morning or evening. Questions have risen concerning the optimal time for obtaining a blood sample for valproic acid (VPA) concentration in relation to the dose. Trough sampling is easily achieved just before a morning daily dose, but the best time to sample after an evening daily dose is unclear, because collecting a blood sample 21 to 24 hours later may be limited by the operational hours of the laboratory. This investigation provides practical guidance regarding blood sample timing. Steady-state plasma VPA concentration-time profiles from 5 published divalproex-ER studies (healthy subjects and epilepsy patients) were analyzed. The concentration-time profile for each subject/patient was expressed as a percentage of his/her trough concentration and summary statistics computed. Typically, when taking divalproex-ER once daily in the morning, a blood sample collected 21 to 24 hours later is expected to have a concentration within 3% of the trough value. Conversely, for divalproex-ER dosed once-daily in the evening, for example 8 PM, a blood draw 12 to 15 hours later (ie, 8 to 11 AM) will give a plasma VPA concentration value that is 18% to 25% higher, on average, than the trough value. However, waiting longer, (for example 18 to 21 hours, ie 2 to 5 PM) will result in concentration values that are merely 3% to 13% higher than trough values, which may provide acceptable information for monitoring purposes. The greatest deviation from trough VPA concentration occurs around the peak, that is 3 to 15 hours after a once-daily divalproex-ER dose; sampling during this time period is recommended only if a clinical need exists to test for a higher VPA concentration. Despite the apparent smoothness of the VPA concentration-time profile after a once-daily divalproex-ER dose, the timing of the blood sample does matter and impacts the proper interpretation of the VPA concentration.
authors.affiliation: Abbott Laboratories, Abbott Park, IL, USA. ronald.reed@abbott.com
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Reed
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dutta
mesh_terms: D000927:Anticonvulsants / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D015203:Reproducibility of Results; D014635:Valproic Acid / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D014635:Valproic Acid