Pharmacokinetic Parameters

Pharmacokinetic Parameters include clearance, volume of distribution, half life, and bioavailability guiding drug dosing and therapy.

• Pharmacokinetics involves the study of how a drug is absorbed, distributed, metabolized, and eliminated by the body.
• The following are key parameters used to describe and quantify these processes:

1. k_e​ (Elimination Rate Constant)

   • The elimination rate constant (ke​) quantifies the fraction of drug removed from the body per unit time.
   • Definition: KE represents the fraction of drug eliminated per unit time.
   • Units: hr⁻¹
   • Equation:
   • $C = C_0 \cdot e^{-k_e t}$
   • Where
     • k_e​ = elimination rate constant
   • In a first-order elimination model (as in the one-compartment model), the rate of drug elimination is proportional to its concentration.

2. (Elimination Half-Life)

   • The elimination half-life is the time required for the plasma concentration of a drug to reduce by 50
   • It is inversely related to the elimination rate constant:
   • $t_{1/2} = \frac{0.693}{k_e}$
   • Half-life is useful for determining dosing intervals and duration of drug action.

3. Vd​ (Apparent Volume of Distribution)

   • The apparent volume of distribution (Vd​) is a theoretical volume that relates the amount of drug in the body to the plasma concentration:
   • $V_d = \frac{\text{Amount of Drug in body}}{\text{Plasma Concentration}}$
   • It reflects the extent of drug distribution into tissues relative to the plasma.
   • A larger Vd​ suggests extensive tissue binding or partitioning.
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4. AUC (Area Under the Curve)

   • The area under the plasma concentration-time curve (AUC) represents total drug exposure over time.
   • It is calculated as the integral of the concentration-time graph:
   • $AUC = \int_{0}^{\infty} C(t)\, dt$
   • AUC is directly related to the dose and bioavailability and inversely related to clearance.

5. ka​ (Absorption Rate Constant)

   • Definition: The rate at which a drug is absorbed into systemic circulation.
   • Units: hr⁻¹
   • Estimation Method:
     • From method of residuals (curve stripping) in extravascular administration
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   • Significance:
     • Determines onset of action
     • Influences Tmax (time to peak concentration)

6. Cl_t​ (Total Body Clearance)

   • Definition: Volume of plasma from which the drug is completely removed per unit time.
   • Units: L/hr or mL/min
   • Equation:
   • $Cl_t = \frac{\text{Dose}}{AUC}$
   • Significance:
     • Key determinant of maintenance dose
     • Influences drug accumulation and steady-state levels
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7. (Renal Clearance)

   • Renal clearance refers to the volume of plasma cleared of the unchanged drug by the kidneys per unit time.
   • It is calculated using:
   • $Cl_R = \frac{\text{Urine Concentration} \times \text{Urine Flow Rate}}{\text{Plasma Concentration}}$
   • Where:
     • U = Urine concentration of drug
     • V = Urine flow rate
     • C_p​ = Plasma concentration
   • Renal clearance helps assess kidney function and the renal route of elimination for a drug.
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