Dosage Calculation: Maintenance Dose and Loading Dose – Elimination Kinetics

00:01 Let's talk about the concept of maintenance and loading doses. Let's use an example of warfarin.

00:07 Warfarin is a drug that requires very close monitoring of therapeutic levels. Here's a patient who takes 1 mg of warfarin. Clearly 1 mg is not going to cut it for this patient, so we need to give him more everyday.

00:23 If he takes 1 mg every single day for 9 days, eventually we will get to the effective concentration that we want.

00:31 But that seems like a long time. Why don't we give him a whole bunch of medication at first, or what we call a loading dose? So here's an example of a patient who took 10 mg on day 1, you can see the concentration really climbs, and then after that we give him 1 mg a day.

00:48 That's the concept of a loading dose. So, in warfarin, we use loading doses all the time.

00:55 The loading dose can be calculated. It is a formula using bioavailablity, the target concentration, and the volume of distribution. So, it's Vd times the concentration divided by the bioavailability.

01:11 Now, the dosing rate, or how often we give the medication, is the clearance times the desired plasma concentration, once again divided by bioavailablity. Let's use bioavailability and volume of distribution to calculate dosing. Here is a case study of a 15 year old woman who has pneumonia.

01:33 She requires an antibiotic called superchillin, which of course doesn't exist.

01:37 It has a volume of distribution of 31 litres, and has an oral bioavailabity of about 55 %.

01:44 The required plasma concentration is 55 mcg/ml. What is the loading dose? Well, let's do the calculations together. We know that the loading dose is the volume of distribution multiplied by the concentration, and divided by bioavailablity. Let's plug in the numbers.

02:04 So you can see here that there is 31 litres times 55 mcg/ml divided by 55 %. That's 31,000 ml, right? So we're going to convert that. It's multiplied by 55 mcg/ml, and the percentage number, we're going to substitude 55 % in the denominator with 100 over 55. The loading dose is therefore 31,000 times 55 times 100 divided by 55, and cancelling out the 55, and cancelling out the millilitres, you get 3,100,000 micrograms or 3.1 grams. This 15 year old girl with pneumonia is getting worse.

02:49 The superchillin will be needed to be given intravenously. Superchillin, Vd of 31 litres, bioavailability 55 %, intravenous bioavailability of 99 %, and a required plasma concentration of 55 mcg/ml. The clearance is 6ml/min.

03:12 What's the dosing regimen of the drug? The dosing rate is the clearance times the concentration divided by bioavailability. The dosing rate is 6 ml/min times 55 mcg/ml divided by 99 %.

03:30 We do the substitution, we cancel out the millilitres, and we get 333 mcg/min, and if we multiply that into hours, we get 20 mg/hour.

03:48 Let's do a study on loading and maintenance dosing. A 66 year old woman had a cardiac arrhythmia which responded to lidocaine. The ideal serum concentration is 3 g/ml. The volume of distribution is 75 litres.

04:02 The clearance is 600 ml/min and the half life is 1.5 hours. The bioavailability is 60 %.

04:10 What's the loading dose? And what's the ideal infusion rate? Okay. So, loading dose, once again, 75 litres is the volume of distribution. The target concentration is 3.

04:23 And the bioavailability is 60 %. So we plug that into our equation, and we do the math, and we end up with 375 mg as your loading dose. The infusion rate is going to be your serum concentration multiplied by your clearance, divided by bioavailability. We are going to get an infusion rate of 3 mcg/ml times 600 ml/min times 100 over 60, which gives us 3000 mcg/min, or 3 mg/min