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In pharmacokinetics, clearance (Cl) is defined as the ‘volume of body fluid cleared of the drug per unit time’ and is expressed in units of volume per time, e.g., L h⁻¹ or mL min⁻¹. Clearance can be determined using elimination rate constant (k) and the volume of distribution (V), i.e., Cl = k × V.

The total body clearance (Cl) is a function of renal (ClR) and non‐renal (ClNR) clearance, and can be expressed as Cl = Cl_R + ClNR. The renal clearance is dependent on kidney function as explained earlier in section 2.7.2. The drug metabolism by the liver, termed as hepatic clearance, represents most of the non‐renal clearance. Total body clearance is, therefore, affected by the renal or the hepatic function or both, as the case may be. For a drug, primarily eliminated unchanged in the urine, any changes in renal function will significantly impact on its clearance. Impaired clearance of the drug may lead to accumulation of the drug in the body and may require adjustment in subsequent dosages to avoid potential toxic effects. The dosage adjustment decisions should not be solely based on renal clearance and must consider total body clearance to ensure the hepatic clearance is taken into consideration (Figure 2.9). Many patients with compromised renal function, such as in chronic kidney disease (CKD) or those with acute kidney injury (AKI) and taking drugs that are primarily eliminated by the kidneys, may require dosage adjustments. The total body clearance of the drug in a patient in association with renal function (as estimated by the creatinine clearance) helps to make personalised dosage adjustments in a patient (section 2.7.2).