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Phenytoin Zero Order Kinetics

The steady-state level may be disproportionately increased, with resultant intoxication, from an increase in dosage of 10 or more. inactive metabolites are excreted in the bile, and then reabsorbed from the intestinal tract and excreted in the urine. The rate of metabolism is dose-dependent, but at levels usually achieved in the generic viagra blood, the rate of oxidation follows zero-order kinetics (i.e. is independent of time concentration). As a result, ethanol metabolism is capacity-limited and is not proportional to the amount of ethanol present in. Table of Contents PHENYTOIN PHARMACOKINETIC MONITORING A. KINETIC PARAMETERS. Bioavailability (F 0.90 – 1.0 Salt Factor (S 0.92 – Phenytoin Na (caps, IV) 1.0 – Phenytoin Acid (tabs, susp) Protein Binding: 90 (87-93) Volume of Distribution (Vd 0.7L/Kg – Adults 1.0L/Kg – Children Half-Life (t. Cpss (SI 40-80 umol/L ( 20umol/L) Time to Steady State: 1-4 weeks (longer with higher doses) Conversion factor to metric: Divide phenytoin zero order kinetics by 4 to convert from umol/L to mg/L B. DOSING. Changes in dosing rate may result in disproportionate, non-linear changes in blood levels, and toxicity may develop. A typical adult can phenytoin zero order kinetics metabolize 7-10g (150-220 mmol) of ethanol per hour (the equivalent of 10oz of beer, 3.5 oz of wine or 1oz of 80 proof spirits). IM Not recommended phenytoin zero order kinetics ORAL : CAPSULES SUSPENSION NG TUBE 15-18 mg/kg PO/NG- given as 200-400 mg q2-3h 5-7 mg/kg/day phenytoin zero order kinetics in one daily dose If 400 mg/day – two doses 5-7 mg/kg/day in 2 to 3 doses may need 2-4 times IV/PO dose hold feeds 2. Pharmacodynamic interactions may also occur with other drugs including CNS depressants Reference: Masters SB (2012e) : The Alcohols (Chapter 23). In: Basic and Clinical Pharmacology. 11th Edition. Katzung BG, Masters SB, Trevor AJ (Editors). Empiric dosing guidelines (use TBW) ROUTE LOADING DOSE. MAINTENANCE DOSE IV 15-18 mg/kg – total dose direct at maximum rate of 50 mg/min. OR Dilute to 5-20 mg/mL with NS give over 15-30 minutes 5-7 mg/kg/day – in 2 to 3 divided doses. Chronic ethanol consumption can induce cyt P450 ; this can increase the hepatotoxicity of acetaminophen due to increased conversion of acetaminophen to reactive hepatotoxic metabolites. Acute alcohol use may inhibit the metabolism of other drugs due to decreased metabolism /or decreased liver blood flow (such. Drug: Phenytoin (Dilantin ) Drug buy viagra Class: Antiepileptic Pharmacokinetics: Phenytoin has dose-dependent kinetics of elimination. Phenytoin is hydroxylated in the liver by an enzyme system that is saturable at high plasma levels, hence small incremental doses may increase the half-life and produce very substantial increases in. References: Porter RJ, Meldrum BS (2012e) : Antiseizure drugs (Chapter 24). In: Basic and Clinical Pharmacology. 11th Edition. Katzung BG, Masters SB, Trevor AJ (Editors). McGraw-Hill / Lange. (Access-Medicine). phenytoin (Dilantin ) Drug: Aspirin Drug Class: Antiinflammatory, Analgesic, Antipyretic, Antirheumatic, Anticoagulant Pharmacokinetics: Aspirin (acetylsalicylic acid). Steady-state therapeutic levels are achieved at least 7 to 10 days (5-7 half-lives) after initiation of therapy with recommended doses of 300 mg/day. When serum level determinations are necessary, they should be obtained at least 5-7 half-lives after treatment initiation, dosage change, or addition or. Post loading dose level and compare to a follow-up level in 2-4 days provides estimate of the accumulation or deficiency of a fixed maintenance dose Seizure Activity: at the time of a seizure, a phenytoin level helps to estimate a threshold for seizure activity 2). These patients also tend to have low serum albumin. In general, aim for therapeutic levels between 20-40 umol/L. D. DOSAGE ADJUSTMENT Phenytoin does NOT phenytoin zero order kinetics demonstrate a proportional relationship between drug levels and dose. References: Burke A, Smyth E, FitzGerald GA (2006) : Analgesic-antipyretic and antiinflammatory agents; pharmacotherapy of gout (Chapter 26). In: Goodman Gilman's Pharmacological Basis of Therapeutics. 11e. Brunton LL (Editor). McGraw-Hill. Reference: wikipedia Drug: Ethanol (Jack Daniels, Budweiser, Cuervo Gold ) Drug Class: CNS Depressant Drug. McGraw-Hill / Lange. (Access-Medicine). Pharmacokinetics, Vd, clearance, first-order, half-life, zero-order, dose-dependent, loading-dose, maintenance-infusion. There may be wide inter-patient variability in phenytoin serum levels with equivalent dosages. Patients with unusually low levels may be non-compliant or hyper-metabolizers of phenytoin. Unusually high levels result from liver disease, congenital enzyme deficiency or drug interactions which result in metabolic interference. Due to zero order kinetics, dosage should NOT be increased by more than 50-100mg increments. OVERDOSE : Hold dosage until levels are back within phenytoin zero order kinetics the therapeutic range then reduce dosage as per above. Urinary excretion of phenytoin and its metabolites occurs partly with glomerular filtration but, more importantly, by tubular secretion. The plasma half-life in man after oral administration of phenytoin averages 22 hours, with a range of 7 to 42 hours.

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