Calculation of the plasma drug levels after a single dose IVinfusion..pptx

Drugs administered by IV route may either be given at once (as a bolus dose) or by slower IV infusion over a definite time such as Phenytoin which must be given slowly, no greater than 50 mg/min (and preferably 25 mg/min or less) in adults. Such drugs are infused slowly through a vein into the blood at a constant rate (zero order input) which allows precise control of plasma drug concentrations.

1. Calculation of the plasma drug levels after a single dose IV infusion Dr Sarad Pawar Naik

2. Intravenous infusion Introduction Drugs administered by IV route may either be given at once (as a bolus dose) or by slower IV infusion over a definite time such as Phenytoin which must be given slowly, no greater than 50 mg/min (and preferably 25 mg/min or less) in adults. Such drugs are infused slowly through a vein into the blood at a constant rate (zero order input) which allows precise control of plasma drug concentrations. The following figure represents the plasma-level time curve for a drug given by constant IV infusion. At time zero, no drug was present in the body after which the drug level gradually increases until it becomes constant (plateau or steady-state). Once the drug has reached the steady-state, the rate of drug leaving the body is equal to the rate of drug entering the body.

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4. A drug has a volume of distribution of 12 L and a K of 0.18 hr . A steady state concentration (Css) of 12 mg/ml is desired. What is the infusion rate needed to maintain this concentration ? How long it takes to achieve 90% and 99% of the Css ? If the elimination rate constant, K, in a patient with a renal impairment is 0.1 hr-1 , what is the infusion rate required to maintain the same Css in this patient? Calculation of the plasma drug levels after a single dose IV infusion. Solution: Equation 2 can be rewritten as K O = Css. Vd . K Therefore: Infusion rate K O = 12 x 12000 x 0.18 = 25920 mg/hr = 25.92 g/hr (b)According to equation 3 C = Css (1- e ) Now, C = 90% of Css, therefore, we can write, 90% of Css = Css (1_e ) 0.9 . Css = Css (1-e ) 0.9 = 1 – e -kt -kt -kt -kt e = 1 - 0.9 = 0.1 -kt [OR] Taking the natural logarithm of both sides –kt = In 0.1 t 90% = In 0.1 -K = = - 2.303 -K - 2.303 0.18 = 12.794 hrs In terms of t 1/2 (0.693 / K = 3.85 hrs), t 90% = 12.794 3.85 = 3.32 t 1/2 -1 Similarly, t 90% = = In 0.1 In 0.1 K 0.18 = = 25.58 hrs 6.645 t 1/2 ( c) The elimination rate constant of the patient is 0.1 hr The infusion rate for this patient to maintain the steady - state concentration of 12 mg/ml is Ko = Css.Vd.K = 12 × 12000×0.1 = 14400 =14.4 mg/hr When the elimination rate constant decreases, then the infusion rate must decrease proportionately to maintain the same Css. However, because the elimination rate constant is smaller (i.e., the elimination half-life is longer), the time to reach Css will be longer. The for this patient is 23.02 hrs , and = is 46.05 hrs. - 1 t 90% t 90%

5. 2) A patient is given an antibiotic having t1/2 of 4 hrs by constant I.V. infusion at a rate of 3 mg/hr. At the end of 36 hours, the plasma drug concentration is 2.2 mg/L. Calculate the total body clearance, Clt for this antibiotic. What is the volume of distribution, Vd , of the drug? Solution: Equation 2 can be rewritten as Vd.K = = Clt Css Ko The plasma sample is taken after 36 hrs of infusion, which time represents 9 times t 1/2 . Therefore, the plasma drug concentration approximates the Css. Clt = K Css = = 3 mg/hr 2.2 mg/L = 1.363 L/hr 1363 ml/hr Volume of distribution, Vd = Clt K = 1363 (0.693/4) = 7870.9 ml = 7.871 Liters

6. Assignment A patient is given an I.V. infusion of an antibiotic at an infusion rate of 26 mg/hr. Blood samples are taken at 10 and 28 hours and plasma drug concentrations are 10 and 11.9 mg/ml respectively. The antibiotic has an elimination half-life of 3 to 5 hrs in the general population. Estimate the elimination half-life of the drug in this patient. A drug whose K = 0.02 hr¹ and Vd =20 liters is infused to a patient at a rate of 3 mg/hr for 8 hrs. What is the concentration of the drug in the body 2 hours after the cessation of the infusion. What is the concentration of a drug after 8 hours after administration of a loading dose of 100 mg and simultaneous infusion of 20 mg/hr (the drug has a t1/2, of 3hrs and a volume of distribution 100 L)? A doctor wants to maintain 2 mg/L of plasma drug level in a patient by administering a loading dose and simultaneously I.V. infusion to get Css of 2 mg/L. If the drug has an elimination rate constant, K = 0.1 hr and Vd = 15 L, what is the required loading dose and what is the required infusion rate? -1

7. An adult male patient (52 years, 70 kg) is to be given an antibiotic by I.V. infusion. According to this model, the antibiotic has an elimination half-life of 2 hours, Vd of 0.9 L/Kg, and is effective at a plasma drug concentration of 10 mg/L. The drug is supplied in 5ml ampoules containing 200 mg/ml. 6)