Lipophilicity highly accumulating substances

A -THC is rapidly distributed to all tissues despite being tightly bound by plasma proteins. A -THC is a highly lipophilic substance and so accumulates in tissue high in lipid content. Traces of A -THC have been found in adipose tissue more than 30 days after the subject smoked a single joint. The terminal half-life of A -THC in plasma ranges from 18 hours to 4 days. 

The associated report concluded, "These data illustrate the efficiency of the blood-brain barrier and the blood-testicular barrier in limiting the access and accumulation of this highly lipophilic substance into brain and testis. ... 

The wide category of halocompounds represents a serious challenge for natural waters, soils and atmosphere. Because of their toxicity combined with high chemical stability, lipophilicity, accumulation-in-the-food-chain capability and long-range diffusivity, several chlorinated and brominated organic substances are included in the list of POPs. 

Chlorophenols are a class of pesticide substances, e.g. fungicides, used for wood preservation, in pulp production and other miscellaneous applications. The substances were introduced in the 1930s and have been used in very large amounts. Today, the consumption has decreased and the substances are banned in many countries. The main active substance in chlorophenol products is pentachloro-phenol (PCP Figure 3.10). The substance is moderately lipophilic and persistent, yet readily absorbed and accumulated in biota and expresses a rather high acute toxicity. The metabolism and breakdown of this envirotoxicant in biota and in the environment are rather slow, resulting in successively dechlorinated metabolites. 

For lipophilic substances this factor can be quite high, but theoretically, there will always be an equilibrium concentration, where no net uptake takes place. The factor is quite versatile as a simple parameter that describes the tendency of a substance to accumulate. 

Even if their absorption is high, the bioavailability of many compounds may be limited by an extensive metabolism that can affect the in vivo activity profile irrespective of its route of administration. Metabolism is vital since it transforms absorbed nutrients into endogenous substances required to maintain body functions for xenobiotics, including phytochemicals, metabolism represents the key body defence mechanism that converts them into less harmful, water-soluble, and thus excretable, compounds. Lipophilic, low molecular weight xenobiotics that are readily absorbed and distributed are difficult to eliminate and thus may accumulate to hazardous levels. Therefore, most lipophilic xenobiotics are metabolized into hydrophilic conjugates that are less likely to pass through membranes and, hence, can be more easily eliminated via the kidney. 

Medicinal products can be applied on the skin to treat local skin diseases (topical application) or to systemically administer an active substance (transdermal application). In the first case, the active substance should accumulate in or even on the skin and display its effect there. When transdermal administration is intended, the active substance should be transported through the skin followed by absorption into the systemic circulation. In the skin the stratum comeum (the most outer layer of 5-50 layers of dead cells, a homed layer of comeocytes, see Fig. 12.1 and Sect. 12.3.1) forms the major barrier for absorption of active substances. The layer is highly lipophilic in nature and is fully impermeable for hydrophilic active substances. Lipophilic active substances, when adequately formulated, may be absorbed via the skin. Typical characteristics which make an active substance suitable for transdermal transport are an octanol-water partition coefficient (expressed as log Pq/w) between 1 and 3 and a molecular mass below 500 Da [10, 11]. Moreover the dose should not exceed 20 mg per day. Hydrophilic active... 

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