A method to determine pharmacokinetic parameters based on andante constant-rate intravenous infusion

Abstract

Abstract On account of the disturbance from the distribution phase, the concentration-time curve of drugs cannot fully reflect the characteristics of elimination, and thus, it is difficult for present methods to obtain ideal pharmacokinetic parameters. This paper presents a method to determine pharmacokinetic parameters based on an andante constant-rate intravenous infusion. A mathematical model of the constant-rate intravenous infusion combined with the elimination of first-order kinetics was established. During infusion, the accumulation tendency of drugs was deduced as $${C}_{t}={C}_{{0}}+({C}_{ss}-{C}_{{0}})\cdot (1-{e}^{-Kt})$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mrow> <mml:mi>C</mml:mi> </mml:mrow> <mml:mrow> <mml:mi>t</mml:mi> </mml:mrow> </mml:msub> <mml:mo>=</mml:mo> <mml:msub> <mml:mrow> <mml:mi>C</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>0</mml:mn> </mml:mrow> </mml:msub> <mml:mo>+</mml:mo> <mml:mo>(</mml:mo> <mml:msub> <mml:mrow> <mml:mi>C</mml:mi> </mml:mrow> <mml:mrow> <mml:mi>s</mml:mi> <mml:mi>s</mml:mi> </mml:mrow> </mml:msub> <mml:mo>−</mml:mo> <mml:msub> <mml:mrow> <mml:mi>C</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>0</mml:mn> </mml:mrow> </mml:msub> <mml:mo>)</mml:mo> <mml:mo>⋅</mml:mo> <mml:mo>(</mml:mo> <mml:mn>1</mml:mn> <mml:mo>−</mml:mo> <mml:msup> <mml:mrow> <mml:mi>e</mml:mi> </mml:mrow> <mml:mrow> <mml:mo>−</mml:mo> <mml:mi>K</mml:mi> <mml:mi>t</mml:mi> </mml:mrow> </mml:msup> <mml:mo>)</mml:mo> </mml:math> using the principle of calculus. Then, the method to determine the pharmacokinetic parameters was summed up. After collecting the blood drug concentration ( C t ) -time ( t ) data from a constant-rate ( v ) infusion period, an exponential regression analysis was conducted to obtain the elimination rate constant ( K ) and plateau concentration ( C ss ). Then, the half-life ( t 1/2 ), apparent volume of distribution ( V d ) and clearance rate ( CL ) were calculated based on the equations, t 1/2 = 0.693/ K , V d = ( v / K )/ C ss and CL = v / C ss , respectively. In addition, an application example of cimetidine in a beagle dog was used to demonstrate the implementation process of the method.