Renal Clearance – Elimination Kinetics

by Pravin Shukle, MD

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    00:01 Let's talk about renal clearance. Now, renal clearance is the rate of excretion in the urine divided by the plasma concentration.

    00:09 So you can see here that the kidneys are going to be very very important in eliminating most of our drugs.

    00:16 Now, we use something called the Cockroft-Gault Formula. So this guy, his name is Donald Cockroft.

    00:24 He is actually a professor at my old university. And what's interesting is, is that when he was a resident, he came up with part of the formula along with his supervising professor. What's really interesting about this guy, aside from being the nicest guy in the world, and a real gem of a person, is that he is actually a respirologist by trade, and he would frequently go over to the nephrologist and torment them and say "How was my formula doing?" So, there was a lot of fun working with him when I was doing my respiratory rotation.

    00:50 Anyway, let's get on to that formula. The formula was calculated out using the creatinine value, as 140 minus the age, times the weight in kilos, divided by the creatinine. That's using the matric numbers. Using the non-matric or standard US numbers, you just have to multiply it in the denominator by 72. Now in women, we do have a correction factor of 0.85. Let's do a case study, and we'll correct for renal disease.

    01:26 William is a 68 year old patient with schizophrenia. His psychiatrist prescribes lithium. The following are the pharmacokinetic parameters. It is a fully bioavailable drug. Okay. The drug is 100% renally excreted with the clearance of 1.8 litres/hour. And these are the other parameters that I have got listed there. What would be the required loading dose for this patient? Let's go through the formula. The loading dose is the volume of distribution times the target concentration, divided by the bioavailablity. Now, I've already said that the bioavailablity is about 100%, so we can ignore that in this equation. The loading dose is the volume of distribution, and the target dose is 63 minus 25 divided by 2, or the average between the minimum effective concentration and the maximum effective or minimum toxic concentration. So we want to target halfway between those two numbers, that's why we are getting an average. So therefore, the loading dose is 51 times 38, which is 1938 mg or about 1.9 g.

    02:43 Now, let's correct for renal disease. What would the maintenance dose per day be? So, the maintenence dose is going to be the serum concentration times the clearance.

    02:57 The maintenence dose is 38 times 1.8 times 24, which will give you 1641 milligrams.

    03:06 Now, let's move on to a patient who has renal failure. You're going to take that original dose, multiply it by the creatinine clearance, and divide it by 100. So let's plug in the numbers again.

    03:22 The corrected dose is the original dose times the creatinine clearance divided by 100.

    03:30 The original dose was 1600, multiplying it by the creatinine which was 66 divided by 100, so your corrected dose is 1056 mg or about 1 g a day. Now that's hard to do. And when you're in a rush on your exam, I'm going to give you an easier way to do the calculation. You should know the hard way to do the calculation, because that's always going to be important. But if you want to do things quick and dirty, I'm going to show you a trick. Intervals don't generally need to change for most drugs.

    04:07 So you can reduce the dosage by the percentage of renal reduction. So let's look at this question again.

    04:14 His renal failure has dropped to one third normal. His previous dose was 300 mg three times a day.

    04:22 What should his new dose be? Should it be A, 100 mg three times a day? Should it be B, 300 mg once a day? Should it be C, 300 mg three times daily? Or should it be D, 100 mg once a day? So the answer is A, 100 mg three times a day. This is the answer that will be correct for the exam.

    04:46 There are those who would argue that B can also be correct, but I want you to focus on what's right for your exam to make things easy, so just divide the dose by the percentage reduction in renal failure.

    About the Lecture

    The lecture Renal Clearance – Elimination Kinetics by Pravin Shukle, MD is from the course Pharmacokinetics and Pharmacodynamics.

    Author of lecture Renal Clearance – Elimination Kinetics

     Pravin Shukle, MD

    Pravin Shukle, MD

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