Pharmacokinetics Language English Format: PDF Price - Tutorsindia

PharmacokineticsMultiple dosing5. A drug is to be administered by repeated bolus i.v. injections twice daily (Dose size = 20mg). The populationaverage volume of distribution and clearance for the drug are 0.71L/Kg and 1.5mL/min/Kg respectively. Thepatient weighs 65Kg. Calculate Css,max and Css,min with this regimen.6. Use the spreadsheet ‘Model multiple i.v. injections’ provided under ‘Pharmacokinetics’ in www.phrData.co.uk to design a dosing schedule that meets the conditions below:--Estimated volume of distribution = 20 L--Estimated K = 0.09 h -1--Peak concentrations to be 5 to 10 mg/L--Trough concentration to be less than 1 mg/LAnswers are available in the final section of the book.10.8 AppendixDerivation of equation: Css,av = F.DCl.τAt steady state, the amount of drug entering the body in one dosage interval is balanced by the amount eliminated inthe same period.Amount entering = F.DAmount eliminated = Average rate of elimination x τ Average rate of elimination = Average body load x K= Average body load x K x τ Average body load = Css,av x V= Css,av x V x K x τ K x V = K x V = Cl= Css,av x Cl x τBring together the terms for amounts entering and eliminated …F.D = Css,av x Cl x τ (Re-arrange)Css,av = F.DCl.τDerivation of equation: Css,max = D/V x 1/(1 – e -Kτ )The proofs of the formulae for peak and trough concentrations are based on the fact that concentrations decline frompeak to trough in the normal exponential manner and then rise again when a new dose is injected. The key point is that,at steady state, the exponential decline over the dosage period is exactly balanced by the rise caused by the next dose.108Download free ebooks at bookboon.com