If intrinsic clearance is very high relative to hepatic blood flow, hepatic clearance approaches which factor?

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Multiple Choice

If intrinsic clearance is very high relative to hepatic blood flow, hepatic clearance approaches which factor?

Explanation:
When the intrinsic clearance capacity of the liver is very high, the rate at which the liver can metabolize a drug is no longer the bottleneck—the delivery of drug to the liver becomes the limiting step. In the well-stirred model, hepatic clearance is given by CL_H = (Q × fu × CLint) / (Q + fu × CLint). If fu × CLint is much larger than Q, the expression simplifies to CL_H ≈ Q. So hepatic clearance approaches the hepatic blood flow rate, meaning the extraction is flow-limited (near 1). Dose or overall bioavailability don’t set CL_H, and the large intrinsic clearance drives CL_H toward Q rather than away from it.

When the intrinsic clearance capacity of the liver is very high, the rate at which the liver can metabolize a drug is no longer the bottleneck—the delivery of drug to the liver becomes the limiting step. In the well-stirred model, hepatic clearance is given by CL_H = (Q × fu × CLint) / (Q + fu × CLint). If fu × CLint is much larger than Q, the expression simplifies to CL_H ≈ Q. So hepatic clearance approaches the hepatic blood flow rate, meaning the extraction is flow-limited (near 1). Dose or overall bioavailability don’t set CL_H, and the large intrinsic clearance drives CL_H toward Q rather than away from it.

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