Pharmacokinetics of Natural Compounds

It is necessary for the rational use of any drug to have a good understanding of the concentrations that will be achieved in the body after its administration. Of particular interest is the question of bioavailability to assess to what degree and how fast the therapeutic agent is absorbed. Whereas there is usually detailed information available about the pharmacokinetics and biopharmaceutics of chemical drugs, this is usually not the case for natural compounds. However, in principle the same concepts apply since only with a good characterization of pharmacokinetics ('what the body does to the drug') and pharmacodynamics ('what the drug does to the body') it is possible to optimize the therapeutic use of the agent. Knowledge of the bioavailability and pharmacokinetics is essential for the correct in-vivo interpretation of in-vitro activities that are sometimes the basis of therapeutic claims. Of particular interest is the question of bioavailability to assess to what degree and how fast compounds are absorbed after administration of natural compounds. Of further interest is the elucidation of metabolic pathways (yielding potentially new active compounds), and the assessment of elimination routes and their kinetics. These data become an important issue to link data from pharmacological assays and clinical effects. Establishing the pharmacological basis for efficacy of natural compounds is a constant challenge due to their complex composition and the ever-increasing list of their putatively active constituents. In vitro assays normally are cheap and relatively easy to perform, but the relevance of the findings is based on a sufficient concentration of active constituents at the site of the action. Thus, these data become an important issue to link data from pharmacological assays and clinical effects. With increasing knowledge of putatively active compounds and availability of highly selective and sensitive analytical methods for certain natural compounds an increasing amount of data on bioavailability and pharmacokinectics have been reported recently. One common problem in the assessment of pharmacokinetic properties of natural products is that frequently the pharmacologically active agents are not known. This presents a dilemma since without clearly identified target compounds it does not make much sense to measure concentrations of the product ingredients. Only if a correlation exists between the concentration of an active component of a natural product and its efficacy and/or safety, pharmacokinetic studies of individual chemical entities are warranted. If this is not possible, an alternative approach for the characterization of natural compounds is the use of pharmacodynamic surrogates, which should be quantifiable and correlate with the therapeutic outcome. These surrogates allow evaluating the overall activity of a complex biological mixture and compare different products. Results from these pharmacodynamic studies may then also be helpful to identify the active ingredients and obtain a better scientific understanding of the pharmacological mechanisms. These studies will lead to appropriate criteria, which can be used to evaluate different natural products and their dosage forms and help to advance the field of herbal medicine from empirical experience to a more rational and safer pharmacotherapy.

This presentation summarizes data available on bioavailability and pharmacokinetics of some commonly used natural compounds. Pharmacokinetic and bioavailability studies that have been conducted for some of the more important or widely used natural products are critically evaluated. A good understanding of their pharmacokinetics and bioavailability is essential in designing rational dosage regimens. Furthermore, various drug interactions are discussed which show that caution should be exercised when combining phytopharmaceuticals with chemical derived active pharmaceutical ingredients.