# PharmPK Discussion - Infusion and loading doses

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• On 24 Sep 2000 at 21:49:19, "viswanath pawar" (vd_pawar.at.rediffmail.com) sent the message
`I am working on a compound which has an half life of about 1.5hrs indogs given by I.V route. I need to maintain ceratin therapeutic bloodlevels for upto 4 hours.I would like to give a loading I.V dose followed by constant infusionfor about an hour or so.How do I calculate the loading dose. And after what time of bolus Ishould start the infusion.Any help I would appreciate.V.Pawar`
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• On 25 Sep 2000 at 15:51:26, ml11439.at.goodnet.com sent the message
`Dr.Pawar,     In order to determine an appropriate loading dose andrate of infusion, you would want to determine the drug'skinetic parameters in the subject(s) of interest. In thesimplest case, one could assume a one compartment modeland determine Ke and Vd.i) Ke and T1/2     Assuming a one compartment model, at least two plasmalevels could be obtained post IV bolus, and the followingequation could be used to determine Ke:         Ke=     [Ln(C1)- Ln(C2)]/[T2-T1]         T1/2=  .693/Ke     Optimally, several plasma concentrations could beobtained and Ke could be solved by linear regression withY= LnCp and X= time. With nonlinear regression, Y= Cpand X= time.ii) Vd     Once Ke is obtained, you can solve for Vd using thefollowing fromula for an IV bolus:         Cp= [Xo/Vd]e-Ket     Using the Ke you obtained in step 1, you can extrapolatethe plasma concentration to time zero to obtain Cpo, theconcentration immediately following the bolus:         Cpo= [Xo/Vd]=  Cp1e+ket1=  Cp2e=Ket2         Vd= Xo/Cpo     Remember to watch your units, such that if the dose wasin mg, then the concentration should be in mg/liter, and theVd will be in liters      Alternatively, if you used linear regression, then theY intercept of the regression equation would be equal to Cpo.iii) Loading dose calculation     Once the Vd has been estimated, the IV bolus loading dosecan be calculated using the follwing formula:     Loading dose=  Cp(desired mg/l) x Vd (liters)iv) Maintenance infusion calculation     The infusion rate can be calculated using the followingformula:     Css= Ko/KeVd     Ko= Css(KeVd)v) Calculation of plasma concentrations     The plasma concentrations can be caculated using thefollowing formula:     Cp= [Xo/Vd]e-ket' + [Ko/KeVd][1-e-Ket'']     Xo= bolus dose (mg)     t'= time after IV bolus     Ko= infusion rate (mg/hr)     t''= duration of IV infusionvi) Multicompartment models and fits     In the two compartment case, the same ideas apply butthe plasma levels are fitted by nonlinear regression, anda Vc along with alpha and beta are calculated. Vc couldbe substituted into equation iii for a loading dose calcualtion,and beta could be substituted into equation iv for Ko calculation.                                 Mike Leibold, PharmD, RPh                                 ML11439.-a-.goodnet.comReferences1) Gibaldi, M., Perrier, D., Pharmacokinetics, New York, Marcel Dekker    19752) Gibaldi, M., Perrier, D., Pharmacokinetics 2nd ed, New York, Marcel Dekker   19823) Wagner, J., Fundamentals of Clinical Pharmacokinetics, Hamilton, Drug    Intelligence Publications 19754) Godfrey, Keith, Compartment Models and Their Application, New York,    Academic Press 19835) Wagner, J.G., Pharmacokinetics for the Pharmaceutical Scientist, Lancaster,    Technomic Publishing Co 1993`
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