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Unformatted text preview: Treating Partial Seizures Carbamazepine-AED- Dosing o 200 mg twice daily with meals Increased in 200 mg increments every other day o Most patients range from 600-1600mg/day However some patients require 2000-3000mg day- Liver metab 98-99% of single dose via 3A4 10-11 epoxide (active)- Inhibitors: ketoconazole, fluconazole, erythromycin, diltiazem- Half-life: 20-50 hours after first dose o 10-25 hours after auto-induction phase complete- Time to peak conc. = 2-24 hours- Suspension ~1.5 hours- Levels: 4-14mcg/ml Oxcarbazepine-AED- Dosing o Start at 300-600mg/day o Usual max daily dose: 2400-3000mg/day o Patients being converted from CBZ, the typical maintenance dose of OXC is 1.5 times the CBZ dose- Oxc is a prodrug rapidly converted to 10-monohydrate derivative (MHD)= active component o via non-inducible cytosolic ketoreductases to MHD- MHD is inactivated by glucuronide conjugation- Eliminated by the kidneys- Plasma half-life is ~9 hours (MHD)- Time to peak conc.: 4-6 hours after dose- Time to steady state conc.: 2-3 days Phenytoin (Dilantin®,PhenyTEK®)-AED- Dosing (F =100%) o PO: 3-5mg/kg (200-400mg) o 15-20mg/kg loading dose o Usual max daily dose: 500-600mg- Exhibits Michaelis-Menten (nonlinear) PK with increased Vd in infants/children (vs. adults) o Greater than expected increase in Css and AUC after an increase in dose o Enzyme responsible for the metabolism or elimination of the drug may start to become saturated- Major metabolite (via oxidation)-HPPA o Undergoes enterohepatic recirculation- Target concentration = 10-20mg/L (total phenytoin) o 5-10 mg/L can be therapeutic; <5mg/L not likely to be effective- Slow oral absorption Dissolution is the rate limiting step- CL and t1/2 = concentration dependent: longer t1/2 at higher [PHY] - Half-life: oral 7-42 hours, (mean 22 hours)- Metabolized: CYP2C9 and CYP2C19- Inhibitors: valproate, ticlodipine, fluoxetine,topiramate- Drugs can displace PHY by competing for binding sites on albumin (~90-95% bound to albumin) o VPA concentration (target: 50-100mg/L) <35 mg/L displacement is minimal >70 mg/L displacement reaches ~40%- EtOH (acute) ↓ phenytoin metabolism and EtOH (chronic) ↑ phenytoin metabolism – Monitor levels within 2-3 days of initiation or dosage change Then at 6-7 days Then once weekly o Maintenance Monitor level every 3-12 months as needed Any time an AED or CYP-affecting drug is added or removed, re-measure level within 2-3 days Lamotrigine - Dosing o Initial Dosing: 25-50mg/day 25 mg every OTHER day if on VPA- Maintenance Dosing: 300-500mg/day 100-150mg/day if on VPA- 55% protein bound- Rapidly and completely absorbed; not affected by food o 90-95% metabolized by liver- Therapeutic range: none reported/none to follow- Half Life: 24-30 hours (monotherapy)- Decreased with PHY or CBZ & Increased with VPA- Does not inhibit or induce liver enzymes- Does not interfere with OCPs; but OCPs may decrease serum concentrations of LMT-...
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This note was uploaded on 11/04/2010 for the course PHAR 3040 taught by Professor Pham,g during the Spring '10 term at UConn.
- Spring '10