Kinetics of drug action in disease states. XX. Effects of acute starvation on the pharmacodynamics of phenobarbital, ethanol and pentylenetetrazol in rats and effects of refeeding and diet composition.

Severely ill patients often do not eat or cannot retain ingested food. Malnutrition occurs frequently in hospitalized individuals and is known to be associated with substantial changes in the pharmacokinetics of certain drugs. On the other hand, little is known about the effect of acute starvation or malnutrition on the pharmacodynamics (concentration-effect relationship) of drugs. To explore the effects of acute starvation on the pharmacodynamics of drugs that depress or stimulate the central nervous system, adult male Sprague-Dawley rats were deprived of food (but not water) for 3 days, whereas control animals had free access to food and water. Slow i.v. infusion of phenobarbital to onset of loss of righting reflex showed that the starved animals required a larger body weight normalized dose and that they had higher phenobarbital concentrations in serum, serum water, brain and cerebrospinal fluid at the pharmacologic endpoint. Refeeding of the rats for 2 or 7 days did not normalize the decreased body weight and serum total protein concentration. The starvation-associated decrease in the sensitivity of the central nervous system to the hypnotic effect of phenobarbital was only reversed slightly by refeeding for 2 days and persisted even after 7 days of refeeding. Acute starvation had no apparent effect on the dose of i.v. infused ethanol required to cause loss of righting reflex and on ethanol concentrations in serum, brain and cerebrospinal fluid at that time. The infused dose and the concentrations of pentylenetetrazol in serum, brain and cerebrospinal fluid at onset of maximal seizures did not differ significantly between starved and control (fed) rats.(ABSTRACT TRUNCATED AT 250 WORDS)