07 - Amisulpride

Amisulpride

Pharmacokinetics CHAPTER 11 Amisulpride Amisulpride plasma levels are closely related to dose with insufficient variation to make routine plasma level monitoring prudent. Higher levels observed in women27–29 seem to have little significant clinical implication for either therapeutic response or adverse effects. A (trough) threshold for clinical response has been suggested to be approximately 100mcg/L30 and mean levels of 367mcg/L29 have been noted in responders. Adverse effects (notably extrapyramidal side effects [EPSEs]) occur at mean levels of 336mcg/L,27 377mcg/L30 and 395mcg/L.28 A plasma level threshold of below 320mcg/L has been found to predict avoidance of EPSEs.30 One review31 has suggested an approximate range of 200–320mcg/L for optimal clinical response and avoidance of adverse effects but a more recent consensus statement32 suggested a target range of 100–320mcg/L. A dose of 200mg a day is sufficient to give a blood level of 100mcg/L33 so this lower threshold is probably too low for a reliable therapeutic effect. In older patients with Drug Target range Sample timing Time to steady state Comments Olanzapine 20–40mcg/L 12 hours 1 week See text Paliperidone20 20–60mcg/L (9-­OH risperidone) Trough 2–3 days oral 2 months depot Target range is the same as that established for risperidone.21 As with risperidone, routine plasma level monitoring is not recommended. Phenytoin7 10–20mg/L Trough Variable Follows zero-­order kinetics. Free levels may be useful in some circumstances. Quetiapine Around 50–100mcg/L? Trough? 2–3 days oral Target range poorly defined. Plasma level monitoring not recommended. See text. Risperidone 20–60mcg/L (active moiety – risperidone + 9-­OH risperidone) Trough 2–3 days oral 6–8 weeks injection Routine plasma level monitoring is not recommended. See text. Tricyclics22 Nortriptyline 50–150mcg/L Amitriptyline 100–200mcg/L Trough 2–3 days Rarely used and of dubious benefit. Use ECG to assess toxicity. Valproate6,7,23–25 50–100mg/L Epilepsy and bipolar Trough 2–3 days Some doubt over value of levels in epilepsy and in bipolar disorder. Some evidence that, in mania, levels up to 125mg/L are tolerated and more effective than lower concentrations. Valproate plasma levels are linearly related to plasma ammonia.26 Table 11.1  (Continued )