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

PHARMD GURU Page 1 THERAPEUTIC DRUG MONITORING OF VALPROIC ACID: GENERAL INTRODUCTION:  Valproic acid is an anti-convulsant, which is used to treat seizures.  It affects chemicals in the body that may be involved in causing seizures.  Sometimes used in combination with other drugs. USES:  Valproic acid is used to treat various types of seizure disorders. Valproic acid is sometimes used together with other seizure medications.  Valproic acid is also used to treat manic episodes related to bipolar disorder (manic depression), and to prevent migraine headaches. MECHANISM OF ACTION:  Valproic acid causes increased availability of GABA, an inhibitory neurotransmitter, to brain neurons.  It may also enhance the action of GABA or mimic its action at postsynaptic receptor sites.  Valproic acid also blocks voltage dependent sodium channels, which results in the suppression of high-frequency repetitive neuronal firing. PHARMACOKINETIC PROFILE: ABSORPTION: Absorption and Bioavailability:  Rapidly and completely absorbed (f = 1).  Oral (fasting) Peak: 1-3 hours.  Meal (food) peak late 6-8 hours.  Enteric coated absorbed delayed 3-5 hrs (lag time 2-4 hrs). DISTRIBUTION: Distribution and Protein binding: Vd = 0.15 L/Kg (0.1 - 0.5 L/Kg) Protein (Albumin) binding get saturated at a concentration >50 μg/ml TDM OF DRUGS USED FOR SEIZURE DISORDERS
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