Pharmacokinetics of Parenteral Injections II

CSS = dose/ total clearance x dosing interval Give the equation for the average conc at steady state (css) Look at equation in ppt CSS max = dose/ volume of distribution How do we calculate the max concentra- - e -ke dosing x interval tion at steady state? Look at equation in ppt - Find out a given dosing regime/ given dose and dose frequency for a given drug What dose the CSS max equation help - Can see if the conc we reach is within us to do? the therapeutic window or if we need to make any adjustments to change max conc. at steady state How do we calculate the min concentra- CSS min = CSS max - dosing/volume of tion at steady state? distribution What is the equation for finding out the concentration once steady state has been reached? Look on slide 7 in ppt Look at practise Q1 & Q2 in ppt Reaching steady state - By doing multiple administrations --> can take some time --> can be a problem in emergencies How else can we reach steady state? 1/4 1. Wash-in - Starting administration - Druh appearing in systemic circulation - Absorption and elimination happening but absorption is > elimination hence why we see an increase in absorption on the graph - First order reaction --> depends on conc. Increase in conc = increase in elimination (elimination rate is slow at the beginning) What are the 3 different regions of the 2. Steady-state conc and time curve? Give a description - Plateau --> real plateau, not between of each min and max - Will have reached a steady state - Rate of infusion = rate of elimination from systemic circulation - conc. at steady state will depend on the properties of the drug i.e. clearance, volume of distribution and dose administered NOT the time to reach steady state 3. Wash-out - Stop infusion - Pure elimination phase - Independent of ROA Ct = Css x e -ket How can we work out the steady state for the wash-out period? Look at slide 11 in ppt Css = R inf/Vd x ke How can we work out the steady state at the steady state period? Look at slide 12 in ppt - Multiply half-life by 4 or 5 because it taken 4-5 half-lives to reach steady state - Short half-life = short infusion enough to reach steady state - Drug with a longer half-life will take 2/4 more time --> if the infusion is shorter How can an estimate for steady state be than this then wont reach steady state calculated? and the equations for steady state won't apply What equation can be used to find out the steady state at anytime during infusion (wash-in and steady-state)? Look at equations on slide 14 in ppt Pharmacokinetics of parenteral infusions 2 methods 1. Bolus injection --> will allow target conc. to be reached. By the time the drug is eliminated the infusion rate will have picked up and will be able to reach target conc. a little faster 2. Wagner's Method A loading dose can ve used in infusions - Have a faster infusion rate around the if we want to reach Css quickly. Explain same time as the half-life of the drug this - Can increase infusion rate but once time = half-life of the drug, need to slow down the infusion --> will allow to reach conc. at steady state --> If we don't slow down infusion rate, risk of going beyond therapeutic window = toxicity Look at slide 15 in ppt - t1/2 is determined from the elimination process - ke is calculated from t1/2 Give some considerations for IV infusion - Vd is calculated from data if steady-state has been reached calculations --> If steady state is NOT reached: 1. Clearance must be calculated using Cl = dose/AUC 3/4 2. Must use the trapezoidal rule to calculate the AUC AUC = dose/ke x Vd - Same as saying: --> D/Clt --> Co/ke How can we calculate the AUC? Can use any of these equations to calculate the AUC after a single I.V administration Look at slide 17 in ppt Look at practise Q3 in ppt 1. Calculate the average of 2 conc and multiply by time difference How do you calculate the bioavailability 2. Area tail = Clast/ke of a drug using the Trapezoidal method? 3. AUC from 0 to t + AUC tail Look at slide 21 & 22 in ppt Look at slides 24, 24 & 24 in ppt Extravascular injections --> I.M, S.C 4/4