The slowest step in this series , which is the rate limiting step, controls the overall rate and extent of appearance of intact drug in the systemic circulation. The rate-limiting ; step will vary from drug to drug. For a drug which has a very poor aqueous solubility, the rate at which it dissolves in the gastrointest inal fluids is often the slowest of all the steps, and the bioavailability of that drug is said to be dissolutiol n-rate limited. In contrast, for a drug that has a high aqueous solubility, its dissolution will be rapid, and the rate at which the drug crosses the gastrointestinal membrane may be the rate -limiting step , termed permeability limited.

In pharmacokinetics, the rate-limiting step is crucial in determining how quickly and efficiently a drug reaches systemic circulation. For drugs with poor aqueous solubility, the dissolution rate in gastrointestinal fluids often becomes the slowest step, making it the rate-limiting factor. This means that the bioavailability of such drugs is primarily controlled by how fast they dissolve, which is referred to as dissolution-rate limited.<br /><br />Conversely, for drugs with high aqueous solubility, dissolution occurs rapidly. In these cases, the rate at which the drug permeates or crosses the gastrointestinal membrane becomes the rate-limiting step. This scenario is known as permeability-limited, where the drug's ability to pass through biological membranes dictates its bioavailability.<br /><br />Understanding whether a drug is dissolution-rate limited or permeability-limited helps in optimizing its formulation and delivery method to improve therapeutic efficacy.