When clearance decreases, the body eliminates the drug more slowly. Since half-life (t½) is directly proportional to the volume of distribution (Vd) and inversely proportional to clearance (Cl), expressed as t½ = 0.693 × (Vd/Cl), a decrease in clearance results in an increased half-life. This means the drug stays longer in the system, prolonging its therapeutic and adverse effects. Understanding this relationship is crucial for dosing adjustments to avoid toxicity.

Reference: Goodman & Gilman’s The Pharmacological Basis of Therapeutics, Brunton et al., 13th Edition.