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Enhancement of Absorption

The process by which drugs administered orally are absorbed into the systemic circulation are complex and involve a variety of mechanisms. Processes including dissolution of the dosage form, solubility in environments with changing pH levels, cell wall permeability and transport, and even pre-systemic metabolism all play a role in the absorption of a drug following oral administration. Most herbal preparations are administered at large doses relative to pharmaceutical agents. For example, most pharmaceutical agents are administered at a dose <1000 mg, while many herbal preparations are administered at doses >1000 mg. thus concomitant administration of an herbal preparation and a drug can lead to significant effects in the gastrointestinal tract. these effects can include altering pH levels, inhibiting cellular uptake or transport, or even blocking metabolic processes. While the potential interactions are complex and varied, the mathematical models that can describe the effects are quite straightforward. For an orally administered drug, there are two parameters that are related to the absorption process, as shown in eqn (5.26). Bioavailability (F) represents the amount of drug absorbed, and the absorption rate (&a) represents the rate at which the drug is absorbed into the systemic circulation.

If the presence of the herbal preparation enhances the extent of absorption, then the herb will increase the effective bioavailability of the drug. this can be modeled using a simple additive model such as

where F represents the absolute bioavailability of the drug in the absence of the herbal preparation, and F1 represents the increase in bioavailability due to the herb. it is important to note that the modeled value of Fherb must be between 0 and 1, therefore F1 must be less than 1 - F in all cases. Setting appropriate boundaries is essential for the modeling to be successful.

If the herbal preparation enhances the rate of drug absorption, a fractional increase in the rate constant ka can be modeled as

where /herb is the fractional increase in absorption rate constant, and is >1. Modeling increases in the absorption rate require multiple concentration measurements between time of dose administration and time at which the peak drug concentration is observed (tmax). It is also possible to have a compound effect where both the amount of drug absorbed and the rate at which absorption occurs can be enhanced. These increases in the rate and extent of absorption can result in elevated drug levels that might lead to toxicity. Therefore, modeling changes in these parameters can help guard against unexpected adverse drug reactions.

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