**2. Absorption, distribution, metabolism, and excretion (ADME) of herbal compounds**

#### **2.1 Absorption of herbal compounds in the gastrointestinal tract**

The impact of oral herbal therapies on individuals and their influencing factors remains understudied. Oral absorption is critical for defining bioavailability of medicinal ingredients from plants. Research on oral absorption is primarily based on animal and cell studies (e.g., Caco-2 cells). Some herbal substances have been assessed for oral bioavailability values, influenced by factors such as gastric fluid solubility, membrane permeability, gastrointestinal tract deprivation, and transporters like P-glycoprotein (P-gp/MDR1/ABCB1). Low or weak intestinal absorption may lead to inadequate oral bioavailability of herbal ingredients, as seen with curcumin. To enhance bioavailability, various formulations like liposomes and nanotechnologybased approaches have been developed [9]. Further research is needed to optimize oral herbal therapies and maximize their therapeutic potential.

*Introductory Chapter: Pharmacokinetics and Drug Metabolism with Special Reference to Herbal… DOI: http://dx.doi.org/10.5772/intechopen.112889*

#### **2.2 Distribution of herbal compounds in the body**

The albumin from human serum (HSA), 1-acid glycoprotein (AGP), lipoprotein, or and globulin are examples of plasma proteins connected to the ADME and pharmacodynamics properties of drugs in the body through bidirectional interactions.

The hydrophobic cavity in HSA is crucial in explaining how it affects the distribution and efficacy of medications. The hydrophobic cavity in HSA can alter the distribution of cells in vivo and in vitro and increase the apparent dissolution of hydrophobic drugs in plasma.

Human serum albumin and berberine, a conventional herbal remedy used to treat gastrointestinal diseases, were examined by Hu et al. The findings showed that the hydrophobic pocket of subdomain IIA was where berberine bound most frequently and that electrostatic forces played a significant role in the interaction of berberine and HSA.

The blood–brain barrier (BBB), which blocks substances from circulating blood from entering the brain through paracellular and transcellular routes, comprises humans' tightly connected brain endothelial cells. These multidrug transporters can prevent harmful circulatory chemicals, including herbal medicines, from making it to the brain. However, these transporters will impede and lessen the efficiency of herbal drugs that impact the central nervous system [10].

#### **2.3 Metabolism of herbal compounds in the liver**

The human gut is where herbal substances are subjected to CYP- and UGTmediated metabolism, which may be a critical factor in influencing intake and bioavailability. Following oral ingestion, herbal essences are vulnerable to presystemic oxidative and/or coupling metabolism, and the presence of several CYPs (in particular CYP3A4), and UGTs is significant in the gut. When absorbing diverse herbal compounds from the core, intestinal CYP3A4 can act as a very effective metabolic barrier without the help of the liver.

Numerous herbal substances often undergo intestinal hydrolysis, yielding pharmacologically active or degraded metabolites. Many herbal treatments' glycosides typically undergo intestinal deglycosylation before being absorbed, and phenolic compounds' aglycones are then sulfated or glucuronidated in the gut and liver. Emodin and sennidin are broken down in the colon to create their pharmacologically effective aglycones [11].

#### **2.4 Excretion of herbal compounds from the body**

Herbal medicines taken orally undergo absorption, metabolism, and subsequent elimination through feces and/or kidneys. Most plant natural products have a short elimination half-life, and their parent chemicals or metabolites can be detected in urine and feces. Urinary excretion is the primary route for eliminating herbal medicine metabolites or parent chemicals, followed by biliary excretion, involving specific drug transporters. For instance, after intravenous administration of 100 mg quercetin, 7.4% was excreted in the urine as a conjugation metabolite, and 0.65% remained unchanged. Quercetin and kaempferol showed recovery rates of 99.7% and 97.4%, respectively. Many herbal medicines are also eliminated through biliary excretion, with fecal recovery rates varying depending on the compound administered [12–16]. The exact role of hepatic transporters in biliary elimination of herbal treatments remains uncertain.
