Digoxin Pharmacokinetics PDF

PHARMACOKINETICS DIGOXIN JOHN M. TOVAR, PHARMD Associate Professor PCOM School of Pharmacy  going Icut exchange Remember...

PHARMACOKINETICS DIGOXIN JOHN M. TOVAR, PHARMD Associate Professor PCOM School of Pharmacy  going Icut exchange Remember every for WE Digoxin 9hr carginorte NAT pump inhibit Digoxin Availability 1 Class and MOA? 921 NAT contractibility Tablets: 62.5, 125, 250 mcg 2 What do we use it for? Elixir: anoxin in HF atib supraventricular arrhythmia mutansloading 50 mcg/mL a No 3 Loading doses? 112 20042 T pt so wld loadanymore due to dose loading NO todaywedon't repenting No better options AT reaured 4 Main adverse events? gone arrhythmia seehalo w digoxin toxicity  Pharmacokinetics Digoxin Absorption Bioavailability F Tablets 0.7 Elixir 0.8 Distribution Ranges from 4 to 9 L/kg population Average value of 7 L/kg is used in practice Beringer P. (2018). Wunter’s Basis Always use IBW Clinical Pharmacokinetics. Lippincott Williams & Wilkins  Pharmacokinetics Digoxin Metabolism Liver and bacteria in large intestine (minimal) Elimination Renal ~ 70% (mainly unchanged) t1/2 = 2 days Beringer P. (2018). Wunter’s Basis Clinical Pharmacokinetics. Lippincott Williams & Wilkins  Pharmacokinetics Digoxin Population-Based CL = (1.303 x CrCl*) + CLm CLm = metabolic clearance = 40 mL/min patients no or mild HF NOHF = 20 mL/min patients moderate to severe HF nay F Patient-Specific CL = MD x 106 x F Css x ! Beringer P. (2018). Wunter’s Basis Css = steady-state plasma concentration in ng/mL Clinical Pharmacokinetics. Lippincott MD = maintenance dose in mg/day Williams & Wilkins ! = dosing interval, in minutes (1440 minutes = 1 day)  Pharmacokinetics Digoxin 1 MD = Css x CL x ! 106 x F K may be calculated Css = steady-state plasma concentration in ng/mL with 1 or 2 levels Goal HF (0.5-0.9) usually use (2 is better). Goal A.Fib (1-2) usually use 1.55hr MD = maintenance dose in mg/day ! = dosing interval, in minutes (1440 minutes = 1 day) 2 CDESIRED= Css x e-kt Beringer P. (2018). Wunter’s Basis t = time must wait until desired level is reached Clinical Pharmacokinetics. Lippincott Williams & Wilkins DOSING CALCULATIONS  Practice Problem BH is a 72-year old, 5’3”, 145-lb female who has a diagnosis of HF for which she currently receives a beta- blocker, ACEI, and a diuretic. She has been hospitalized Because of half-life is 3 times in the past year for HF; at this time, her about 2 days, we always physician wishes to initiate digoxin therapy. Her current dose it once daily. creatinine is 1 mg/dL. Calculate a maintenance of digoxin tablets to be given to BH to achieve a satisfactory steady-state serum digoxin level.  Practice Problem Two months later, BH has steady state serum digoxin level drawn. The laboratory reports this value as 0.5 Now that you have a ng/mL. Although this values is within the therapeutic level, you can use it to range for HF, BH’s physician desires to increase the dose to achieve a slightly higher serum concentration. calculate the patient’s Calculate a new maintenance dose for BH that will real clearance. achieve a serum concentration of 0.8 ng/mL. Calculate a new maintenance dose.