Lecture 5 — Bioequivalence and Drug Clearance
Bioequivalence and bioavailability
• A generic drug formulation is considered bioequivalent to a reference product when the products behave equivalently in the body. The lecture illustrates the difference between the brand name Panadol and the active ingredient paracetamol.
• Bioavailability is generally measured during drug-product development rather than routinely in an individual patient. Understanding differences between formulations and administration routes helps guide dose adjustments when switching products or routes.
Clearance: meaning and units
• Clearance (CL) describes the efficiency of irreversible drug elimination. It is the volume of blood or plasma effectively cleared of drug per unit time, for example mL/min.
• Clearance may occur through metabolism (conversion of parent drug to metabolites) or excretion (physical removal of unchanged drug). A drug molecule can count as cleared from the parent-drug pool after glucuronidation even before its metabolite leaves the body.
• Movement of unchanged drug into fat or other tissue storage does not itself count as irreversible clearance.
Routes and types of clearance
• Excretion may involve urine, intestinal contents, expired air, sweat, or saliva.
• Total or systemic clearance represents clearance through all elimination pathways. Renal clearance is the part attributable to the kidneys and is particularly relevant when a drug is eliminated primarily by renal excretion.
Estimating clearance
• For accurate calculation of total clearance from administered dose, the lecture emphasizes intravenous administration because IV bioavailability is 100%.
• When IV administration is not possible, apparent (oral) clearance may be estimated. Because the fraction absorbed is uncertain, apparent oral clearance can exceed true systemic clearance.
• Renal clearance can be estimated using the total amount of unchanged drug excreted in urine (Ae) and systemic drug exposure. The original lecture includes equations as figures; no equation graphic is recreated here.
Why clearance matters
• Clearance helps individualize drug dosing by taking into account how efficiently a person eliminates a drug.
• Clearance is related to both distribution characteristics and elimination rate; these may differ between patients.
Prepared for Dear Study. Review alongside the original university PDF for figures and slide-specific details.
