What is the pharmacokinetics of phenytoin?
Hepatic microsomal enzymes primarily metabolize phenytoin. Much of the drug is excreted in the bile as an inactive metabolite, which is then reabsorbed from the intestinal tract and ultimately excreted in the urine. Less than 5% of phenytoin is excreted unchanged in the urine.
How do you titrate phenytoin?
Adjustments
- If the phenytoin concentration is <7 ug/mL, the dose may be increased by 100 mg/day.
- If the phenytoin concentration is 7-12 ug/mL, the dose may be increased by 50 mg/day.
- If the phenytoin concentration is >12 mg/mL, the dose may be increased by 30 mg/day.
Why is the maximum infusion rate of phenytoin 50 mg min?
Because of the increased risk of adverse cardiovascular reactions associated with rapid administration, intravenous administration should not exceed 50 mg per minute in adults. In pediatric patients, the drug should be administered at a rate not exceeding 1-3 mg/kg/min or 50 mg per minute, whichever is slower.
How do you calculate phenytoin Vmax?
Significant inter-patient variability may exist for many of the pharmacokinetic parameters. Here are some reported ranges: Vd: 0.52 – 0.78 L/kg Vmax: 6 – 8 mg/kg/day Km: 5.4 – 6.8 mg/L….Phenytoin dosing guidelines.
| Vmax | Maximum rate of drug metabolism |
|---|---|
| Km | Concentration at which the rate of drug metabolism is 50% of Vmax |
What calculation is used to correct total phenytoin levels for a low albumin concentration?
The “Sheiner-Tozer Equation” is the official name of this correction. This updated formula uses an albumin coefficient of 0.275, and 0.2 for patients with renal failure (see Evidence for details).
What happened when phenytoin given with TCAs?
Phenytoin may act through a similar mechanism as lidocaine, although experimental studies suggest that it does not compete directly for the same sodium channel binding site as TCAs. Allosteric modulation of the TCA binding site may occur in the setting of phenytoin use.
How is phenytoin metabolised?
Phenytoin is metabolized by cytochrome P450 (P450) enzymes primarily to 5-(p-hydroxyphenyl-),5-phenylhydantoin (HPPH), which may be further metabolized to a catechol that spontaneously oxidizes to semiquinone and quinone species that covalently modify proteins.
How do you adjust phenytoin levels?
A rough guide to making an adjustment to the daily dose that should increase a serum level without leading to supratherapeutic / toxic levels is: If the phenytoin concentration is < 7 mcg/mL, the dose may be increased by 100 mg/day. If the phenytoin concentration is 7-12 mcg/mL, the dose may be increased by 50 mg/day.
What is the maximum infusion rate for phenytoin?
The maximum IV infusion rate of phenytoin sodium injection is 0.5 mg/kg/min for neonates, 1 mg/kg/min for children and adolescents, and for adults, the maximum infusion rate is 50 mg/min.
How do you load phenytoin IV?
Phenytoin IV administration
- Give phenytoin over 30-40 minutes (rate <50mg/minute).
- Ideally, administer undiluted via a syringe pump through a large gauge needle or IV catheter into a large forearm vein.
Why is phenytoin used as a therapeutic calculator?
About This Calculator. Due to its narrow therapeutic index and non-linear pharmacokinetic profile, phenytoin therapeutic drug monitoring is recommended. Because phenytoin is highly protein bound and only unbound drug is capable of crossing the blood-brain barrier to exert its pharmacologic effect, unbound…
Why are phenytoin levels more relevant than total levels?
Because phenytoin is highly protein bound and only unbound drug is capable of crossing the blood-brain barrier to exert its pharmacologic effect, unbound (free) phenytoin levels may be more clinically relevant than total levels to maximize efficacy and minimize toxicity. 3 , 4.
When to give a loading dose of phenytoin?
These loading doses may be given on initiation of therapy, or in response to a subtherapeutic drug level in patients at high risk for seizure activity. The basis of loading dose calculations involves a drug’s volume of distribution (Vd).
What is the winter Tozer equation for phenytoin?
The Winter-Tozer equation was developed to help clinicians estimate an unbound (free) phenytoin concentration based on a total phenytoin level and a serum albumin level. In patients with hypoalbuminemia, a corrected equation must be used to account for reduced phenytoin protein binding.