C3.1 R4(e): Perform & document a pharmacokinetic interpretation (OTHER drug)

Clinical Pharmacy Note RE: Valproic Acid (VPA) Level *My notes

ID: 55 yo male with psychosis (wt = 50kg)
prescribed valproic acid as augmentation to his antipsychotic for persistent symptoms of agitation 

  1. Sept 23 Labs:
    AST: 64 ↑     ALT: 109 ↑    GGT: 268  ↑   ALP: 71   Total bilirubin: 10   Alb: 35g/L
    Patient is also hepatitis C+. 
  2. Sept 14 Labs (was on Divalproex 500mg BID):
    AST: 76 ↑      ALT: 123 ↑    GGT: 441 ↑    ALP: 75
  3. VPA level: 515 (reference range: 350- 835 umol/L)
    valproic acid monitoring to assess for toxicity and to assess if room to grew for efficacy if clinically indicated. CPS: A good correlation has not been established between daily dose, total serum valproate concentration and therapeutic effect
    – drawn at 1000 hr on Sept 26, 2016 (12 hours after 2200 hr dose on Sept 25)
    – valproic acid was ↑ from 1500mg PO HS to 1750mg PO HS on September 21, 2016
    (Max dose: 60mg/kg/day = 3000mg)


  1. All doses were given on time
  2. Level was taken at steady state (half-life increases in hepatic impairment but questionable clinical significance, as per UofK PK manual)
    Lexi-comp: Half-life in adults: 9-19 hours (5 half-lives: ~1.875-3.95 days)
    University of Kentucky Pharmacokinetic Manual: Protein binding decreases in patients with hepatic impairment
    In order to do free VPA level at SPH: physician needs to fill a form stating reason for monitoring. 
  3. Level was drawn on time appropriately.
    University of Kentucky Pharmacokinetic Manual
    – trough levels (within 30 mins prior to dose)
    – preferably before AM dose, due to effects of diurnal variation on clearance
    St. Paul’s reference range: based on 12 hours post-dose
    Handbook of psychiatric drugs (2004 edition) : “Serum drug levels should be drawn 12 hours after the previous dose and are usually drawn in the morning before AM dose.” 
  4. Valproic acid level is within normal reference range.
  5. Currently unsuitable to interview, as per nurses about side effects and efficacy

P: Suggest

  1. Continue valproic acid 1750mg PO HS
    ?frequency of valproic acid – Lexicomp: >250mg should be in divided doses.
    ?Compliance issues as patient has frontal lobe syndrome and refusing meds in hospital. Half-life is 9-19 hours but longer in hepatic impairment. Patient appears to be tolerating medication and psychosis seems to be improving. Difficult to assess patient’s baseline cognitive function (MOCA on admission: 8/30)
  2. Monitor for side effects: ataxia, abnormal gait, nausea, vomiting, anorexia and hepatotoxicity (e.g. jaundice)
  3. Monitor LFTs, INR, albumin and bilirubin regularly every 6 months

For levels:

  • Look at the patient’s whole clinical picture (e.g. size, weight, age, fragility, clinical stability)
  • Look at all the medications patients are on
  • Look to see if there are any recent medication and clinical changes (poly-pharmacy)



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