Pentobarbital partition coefficient

Compounds of similar structure and ionization may have very different partition coefficients. For example, thiopental and pentobarbital are very similar in structure and acidity but have very different lipophilicity (Fig. 3.5), and hence their disposition in vivo is different (see below). 

Barbiturates that have substituents in the 5 position promoting mure rapid metabolism (e.g.. by increasing the lipid/ water partition coefficient) than the intermediate group in-dude Pentobarbital-Sodiunit USP, sodium S-ethyl-S-( I methylbutyDbarbiturate (Nembutal) Secobarbital, IJSP, S-illyl-S-(l-melhylbutyl)barbiluric acid (Seconal) and the sodium salt sodium secobarbital. 

The sulfur analogue of pentobarbital, called thiopental (Figure 3.14), is widely used in operating theatres for the induction of general anaesthesia. Thiobarbiturates of this type have a much higher partition coefficient than the oxobarbiturates used as hypnotics (see Chapter 2). As a result, thiopental, when administered intravenously to a vein in the back of the hand, can in a matter of seconds induce unconsciousness that lasts for several minutes. This is sufficient time for the anaesthetist to introduce an airway to the patient and commence general anaesthesia. 

A commercial CE system and a micropacked capillary was used to separate N—, O—, and S-containing heterocyclic compounds. Migration time reproducibility, linearity, and detector response was found to be comparable to HPLC. A study of the heterocyclic compound s elution order followed that predicted by the octanol-water partition coefficients (354). While chiral CEC provides improved resolution and higher efficiencies, additional work is needed since chiral CEC capillaries are not available commercially. The separation principles and chiral recognition mechanism for the separation of enantiomers have been reviewed (355). Furthermore, a comprehensive collection of drug applications and other compounds of interest has been reported (356). Direct enantiomeric separations by CEC were studied using a capillary packed with alpha-1-acid glycoprotein chiral stationary phase (357). Chiral resolution was achieved for enantiomers of benzoin, hexobarbital, pentobarbital, fosfamide, disopyramide, methoprolol, oxprenolol, and propanolol. The effects of pH, electrolyte concentration, and con-... 

The low concentration of protein in the interstitial fluid has been suggested as another factor which may reduce the distribution of some substances in the central nervous system. Lipid soluble compounds, such as methyl mercury which is toxic to the central nervous system (see Chapter 7). can enter the brain readily, the facility being reflected by the partition coefficient. Another example which illustrates the importance of the lipophilicity in the tissue distribution and duration of action of a foreign compound is afforded by a comparison of the drugs thiopental and pentobarbital (figure 3,5). These drugs are very similar in structure, only differing by one atom. Their pKa values are similar and consequently the... 

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