Drug safety pharmacokinetic interactions

Both pharmacodynamic and pharmacokinetic interactions may have positive effects, such as increasing the efficacy or bioavailability of drugs or botanicals. Such positive therapeutic interactions are not covered in this text, unless the interaction also poses a safety concern. 

Drug Levels in Plasma. Drug levels may also be measured in a clinical trial. Such levels are usually part of a pharmacokinetic analysis but also provide important safety data. This information would be particularly relevant in cases of suspected or actual drug overdosage, drug interactions, to correlate medicine levels with toxic events, or in other situations. It must be clarified whether free levels of the drug and/or the protein bound will be measured by the laboratory. 

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. 

The most common adverse effects associated with nelfinavir are diarrhea and flatulence. Diarrhea often responds to antidiarrheal medications but can be dose-limiting. Nelfinavir is an inhibitor of the CYP3A system, and multiple drug interactions may occur (Tables 49-3 and 49-4). An increased dosage of nelfinavir is recommended when co-administered with rifabutin (with a decreased dose of rifabutin), whereas a decrease in saquinavir dose is suggested with concurrent nelfinavir. Co-administration with efavirenz should be avoided due to decreased indinavir levels. Nelfinavir has a favorable safety and pharmacokinetic profile for pregnant women compared with that of other Pis (Table 49-5) there is no evidence of human teratogenicity. 

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