1. ALLIE PUNKE PHARMCOKINETICS

2. PHENYTOIN

3. THE BASICS What is the volume of distribution: Regular floor patient: 0.6-0.8 L/kg Critically ill patient: 0.8 L/kg What percent is protein bound? 90%, 10% unbound Max rate of infusion of phenytoin? 50 mg/min Max rate of infusion of fosphenytoin? 150 mg PE/min

4. THE BASICS SE of giving phenytoin too fast? Hypotension & bradycardia…caused by propylene glycol What should phenytoin ONLY be mixed with? NS. Phenytoin or fosphenytoin can be given IM? Fospheynytoin Therapeutic range? Total: 10-20 Free: 1-2 What is special about the kinetics of phenytoin? Saturable kinetics

5. THE BASICS You are reviewing medications for a long-term care facility. One of your new patients, NP, is in stable condition and her medication regimen includes phenytoin. How should we avoid the interaction of phenytoin with her enteral feeds? 1. Hold feeds 1-2 hours before/after dosing phenytoin 2. IV phenytoin 3. Bolus feedings & just separate the dosing of phenytoin from feedings.

6. PHENYTOIN When reviewing labs, you notice that one of your patients in the ICU is on phenytoin with a level of 8. What other information should we look at to interpret this dose? Albumin Timing Overall status of patient Interactions- CYP2C9 Inducers: Rifampin, chronic alcoholic, phenobarbital Inhibition: Cimetidine, omeprazole, fluconazole, amiodarone, isoniazide.

7. PHENYTOIN HS (100 kg, 69 in) is admitted due to status epilepticus. What LD of phenytoin should we give her? 1. What weight do we use? Adjusted body weight (>130% of IBW) IBW: 66.2 kg ABW: 77.4kg 2. What LD dose (mg/kg) should we use in this patient? LD=20 mg/kg*77.4kg=1550 mg 3. How fast can we give it? 30 minutes (1550 mg 50 mg ---------------------= ------------- xmin 1 minute 4. When/should we draw a level?

8. PHENYTOIN HS (100 kg, 69 in) is admitted due to status epilepticus. She is on phenytoin at home and has a phenytoin level of 4. What LD should we give her? LD(partial)=(20-4)*0.8L/kg*77.4 kg= 990 mg

9. PHENYTOIN HS (100 kg, 69 in) is admitted due to status epilepticus. She is on phenytoin at home and has a phenytoin level of 4. Albumin level=2.3. CrCl=57. What LD should we give her? LD(partial)=(20-7)*0.8L/kg*77.4=804 mg Corrected Phenytoin concentration: 4 ------------=7 0.2(2.3)+0.1

10. PHENYTOIN HS is now stable and is in the ICU for close observation. What should HS’s daily maintenance dose be? 4-8 mg/kg/day 4-6: floor/amb care patients 6-8: critically ill 6 mg/kg*77.4 kg=464 mg

11. PHENYTOIN In your ambulatory clinic, you adjusted the phenytoin dose appropriately for a patient. When should a level be drawn? A. The next day B. At the end of the dosing interval (>12 hours) C. 2-4 weeks D. 5-7 days

12. PHENYTOIN A patient with severe renal dysfunction (CrCl<10) has a phenytoin level of 7. Albumin level=2.7. What is her corrected phenytoin concentration? Corrected phenytoin: 7 ---------=18.9 0.1(2.7) +0.1

13. PHENYTOIN A patient is being managed with phenytoin. Because of concern for toxicity (uncoordinated movement, arrhythmias), a level was drawn (phenytoin=32). What should be done? A. Hold the next two doses B. Decrease dose by 50-100 mg/day and hold for 1-2 days C. Stop phenytoin, get daily levels, and restart when level is <20. D. Continue normal dose, symptoms most likely not due to phenytoin.

14. QUESTIONS? GOOD LUCK!