Pentobarbital distribution

A discussion of all the reasons for this phenomenon is beyond the scope of this chapter, but a simple example will illustrate the concept. Highly lipid-soluble drugs, such as pentobarbital, are preferentially distributed into adipose tissue. The result is that plasma concentrations are extremely low after distribution is complete. When the apparent volumes of distribution are calculated, they are frequently found to exceed total body volume, occasionally by a factor of 2 or more. This would be impossible if the concentration in the entire body compartment were equal to the plasma concentration. Thus, Vd is an empirically fabricated number relating the... 

What is the difference between the drugs thiopental and pentobarbital and how would it affect their absorption and distribution ... 

The difference between the two drugs pentobarbital and thiopental is that thiopental has a sulfur atom at position 2 whereas pentobarbital has an oxygen atom. Consequently thiopental is more lipophilic and therefore will be more readily absorbed and will distribute more rapidly into fat tissue. 

Pentobarbital is 65% plasma protein bound with a volume of distribution of 0.5 to 1.0 L/kg.6 After intravenous administration, estimates of the plasma half-life have averaged between 20 and 30 h. Amobarbital is similar to pentobarbital in the degree of plasma protein binding (59%) with a slightly larger volume of distribution (0.9 to 1.4 L/kg). The plasma half-life, however, is dose dependent, with a range of 15 to 40 h.6 Phenobarbital is approximately 50% plasma protein bound... 

Jaeger RJ, Murphy SD. 1973. Duration of action distribution and metabolism of pentobarbital or hexobarbital after 1, 1-dichloroethylene, corticosterone or acrolein. Fed Proc 32(3 Part 1) 320. 

Benowitz NL, Jones RT. Effects of delta-9-tetrahydrocan-nabinol on drug distribution and metabolism. Antipyrine, pentobarbital, and ethanol. Clin Pharmacol Ther... 

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... 

All three barbiturates are primarily eliminated by hepatic metabolism and renal excretion of inactive metabolites a small fraction of thiopental undergoes desulfuration to the longer-acting hypnotic pentobarbital. Each drug is highly protein bound (Table 13-2). Hepatic disease or other conditions that reduce serum protein concentration will decrease the volume of distribution and thereby increase the initial free concentration and hypnotic effect of an induction dose. 

Quantitative distribution measurements for positron-emitting radionuclides in a wide selection of organs and tissues as a function of time after injection can, at present, best be obtained by dissection studies. We are currently carrying out such studies in rats, in which the N-concentrations of 14 major organs and tissues are measured at a series of time points up to 50 min after intravenous injection of N-labeled L-amino acids or [ N]ammonia. As an example of the data obtained in these studies, relative concentrations of the brain, heart, and pancreas of pentobarbital-anesthetized adult male Sprague-Dawley rats are plotted... 

Donelli MG, Colombo T, Garattini S. Effect of cyclophosphamide on the activity and distribution of pentobarbital in rats. Biochem Pharmacol (1973) 22,2609-14. 

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