Bioavailability Blood vessel

This pattern is not true for all drugs, however. For example, diazepam and chlordiazepoxide are unstable at a pH of 7.4 and tend to crystallize in tissue when given intramuscularly (14, 17, 18). Therefore, they are less bioavailable when given intramuscularly versus orally. Their absorption also tends to be erratic and variable, depending on where the injection was given (i.e., near blood vessels, in fat, or in muscle), as well as slower and less complete. 

Sumatriptan (Imigran) selectively shmulates a subtype of 5-hydroxytiyptaminej-receptors (called 5-HTjg jp-receptors) which are found in cranial blood vessels, causing them to constrict. It is rapidly absorbed after oral administration and undergoes extensive (84%) presystemic metabolism but bioavailability by the s.c. route is 96%. The t) is 2 h. 

We will refer to oral absorption as the movement of dmg across the outer mucosal membranes of the GI tract [112], whereas oral bioavailability is that fraction of the dose that reaches the general circulation unchanged [113]. The general circulation is defined experimentally in terms of a blood vessel in the peripheral circulation. 

As in humans ethical constraints limit sampling sites to peripheral blood vessels, absorption cannot directly be estimated. Hence, the absorption rate (ka, fe0i) as calculated from peripheral plasma concentration data by compartmental or noncom-partmental models reflects rather an oral bioavailability rate, unless any gut wall and liver first-pass elimination is ruled out [112]. 

Cocaine is a tertiary amine, methamphetamine a secondary amine, and amphetamine a primary amine. Typical pK values for [RjNHjT [RjNHj], and [RNH3] are, respectively, 9.76, 10.66, and 10.63. The salts are water soluble and hence more easily ingested, but they are nonvolatile, so difficult to inhale. The free bases are less water soluble but relatively volatile, hence easier to inhale. Since the lungs are richly supplied with blood vessels, inhalation results in higher and faster bioavailability of the drugs. 

Recently, the biological impact of dietary polyphenols has been associated with the endothelial metabolism of NO. In particular, it has been shown that mono-O-methylated flavanols and other flavonoids by inhibition of endothelial NADPH oxidase suppress the formation of superoxide radical, that otherwise eliminates NO via diffusion-controlled formation of peroxynitrite (Steffen et al, 2008). Such a mechanism, preserving or enhancing the bioavailability of NO, may underlie the improvement of vascular endothelial function by certain flavonoid structures and its metabolites via, for instance, dilation of arterial vessels and lowering of blood pressure (Steffen et al, 2008). 

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