Pharmacokinetics of Botanical Products

Department of Pharmaceutics, Center for Food Drug Interaction Research and Education, University of Florida, Gainesville, Florida, US.A. 

A general disillusionment with conventional medicines, coupled with the desire for a natural lifestyle has resulted in an increasing utilization of herbal medicinal products (HMPs) across the developed world. Sales of botanical products in the United States have increased sharply in recent years, according to industry reports. An estimated 4 billion was spent in health food stores in 2000 for botanical products in bulk, as well as capsules, tablets, extracts, and teas (1 ). A similar trend is noted for European countries (5). 

For the majority of these multicomponent mixtures, the active constituents are often unknown. In other words, a substance that is detectable in body fluids is not necessarily the active compound of an extract. Further, the different compounds will have a different bioavailability, thereby complicating the design of pharmacokinetic studies with HMPs. Natural compounds are often prodrugs that are metabolized in the digestive tract. Moreover, HMPs can contain large polar molecules that might be expected to have poor and unpredictable bioavailability (7). 

biloba L. is a member of the Ginkgoaceae family, a gymnosperm that has survived unchanged from the Triassic period. In traditional Chinese medicine, the seeds (nuts) of G. biloba were used as an antitussive, expectorant, and antiasthmatic, and in bladder infection (20). In China, the leaves of G. biloba were also used for the treatment of asthma and cardiovascular disorders (21). Today, standardized concentrated extracts prepared from the leaves of G. biloba are used for the treatment of peripheral circulatory insufficiency, cerebrovascular disorders, geriatric complaints, and for Alzheimer dementia. For a more extensive treatment, readers are referred to the many authoritative reviews available, e.g.. Refs. (22-27). 

Both human and animal pharmacokinetic studies have been done on ginkgo flavonol aglycones (quercetin, kaempferol, and isorhamnetin) and terpene trilactones (ginkgolide A and B and bilobalide). 

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However, the information derived from a detailed pharmacokinetic study will help to anticipate potential botanical product-drug interactions, to optimize the bioavailability, the quality, and hence the efficacy of herbal medicines, to support evidence for the synergistic nature of herbal medicines, and to better appreciate the safety and toxicity of the plant. Because pharmacokinetic studies with herbal medicines are often complicated by their chemical complexity and by the fact that the active compounds are often unknown, it could be one future issue to assess bioavailability by measuring surrogate parameters in plasma or tissue instead of directly assaying putative active compounds in the blood. In summary, to use HMPs in an evidence-based approach and to achieve the status rational phytomedicine, more experimental studies are needed to characterize the bioavailability and pharmacokinetics of botanical products. 

Similar to the challenges outlined in Chapter 2, the fact that most Chinese herbal medicines are complex mixtures of multiple active constituents further complicates the interpretation of study data, as well as extrapolation to other botanical products. Japanese Kampo (traditional Chinese herbal mixtures) prescriptions have been used for many years to treat different chronic conditions and are presently manufactured in Japan as drugs with standardized quantities and qualities of constituents. Homma et al. (51) evaluated the effect of three commonly used Japanese Kampo prescriptions, Sho-saiko-to (Xiao Chai Hu Tang), Saiboku-to, and Sairei-to, on prednisolone pharmacokinetics in humans. All three botanical prescriptions contain glycyrrhizin, a strong inhibitor of 11-p-hydroxysteroid dehydrogenase. Chen et al. (52) had shown that glycyrrhizin decreased plasma clearance and increased AUC and concentration of prednisolone. 

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