Tiêu đề 11. TDM OF DRUGS USED FOR SEIZURE DISORDERS.pdf ✅

PHARMD GURU Page 2 METABOLISM: >95% hepatic metabolism. EXCRETION:  1-3% renal excretion.  Oral clearance (Cl/F) is 7-12 ml/h/kg for adults.  In children 6-12 years old, oral clearance) 10-20 ml/h/kg. HALF-LIFE (t1/2):  Half-life is 12-18 hours in adults.  Half-life for children 6-12 year old is 6-8 hours. ADR/TOXIC EFFECT: Adverse effect related to plasma drug concentration: PLASMA LEVEL SYMPTOMS >75 mcg/L Ataxia, sedation, lethargy. >100 mcg/L Tremors. >175 mcg/L COMA, stupor. DRUG INTERACTIONS:  Phenytoin, lamotrigine, rifampin, and carbamazepine can increase valproic acid clearance and decrease valproic acid steady-state serum concentrations.  Cimetidine, chlorpromazine, and felbamate are examples of drugs that decrease valproic acid clearance and increase valproic acid steady-state concentrations. THERAPEUTIC RANGE: Dose: 50 – 100 μg/ml  Generalized seizures: 30 – 60 μg/ml  Partial seizures: 55 – 100 μg/ml TOXIC RANGE: > 100 μg/ml
PHARMD GURU Page 3 CONTRAINDICATIONS:  Contraindicated in:  Liver disease.  Urea cycle disorders.  Known porphriya.  Pregnancy. MONITORING PARAMETERS:  The goal of therapy with anticonvulsants is to reduce seizure frequency and maximize quality of life with a minimum of adverse drug effects.  Patients should be monitored for concentration-related side effects (ataxia, sedation, lethargy, tiredness, tremor, stupor, coma, and thrombocytopenia) as well as gastrointestinal upset associated with local irritation of gastric mucosa (nausea, vomiting, and anorexia).  Elevated liver function tests, increased serum ammonia, alopecia, and weight gain have been reported during chronic Valproic acid treatment.  Serious, but rare, idiosyncratic side effects include hepatotoxicity, pancreatitis, pitting edema, systemic lupus-like reactions, and leucopenia with bone marrow changes. DOSAGE ADJUSTMENTS:  For renal impairment: No adjustment is necessary, protein binding is reduced and may lead to inaccurate measurement of total valproate concentrations.  For Hepatic impairment: It is not recommended. It is contraindicated. SAMPLING TIME:  3-5 days may be required to reach the steady state concentration.  Trough samples are taken, but sometimes both trough and peak samples are withdrawn. ASSAYS USED:  Immunoassays.  HPLC.