THE EFFECTS OF ANTACIDS ON THE ABSORPTION OF ORALLY ADMINISTERED PENTOBARBITAL IN THE RAT

¹ The Departments of Medicine and Pharmacology, Clinical Pharmacology Study Unit, University of Kansas Medical Center, Kansas City, Kansas

Studies were done in rats to evaluate possible interactions between antacids and pentobarbital administered by gastric intubation. Magnesium and aluminum hydroxides both retard gastrointestinal sodium pentobarbital absorption, lowering blood levels and preventing or delaying the onset of sleep. Magnesium hydroxide, by raising the gastric pH, shifts the pentobarbital to the ionized, unabsorbable form. Aluminum hydroxide acts by retarding gastric emptying, markedly increasing the fluid volume and pentobarbital retained in the stomach. This property, which greatly exceeds the gastric retention after atropine, is shared by dissociable aluminum salts and another trivalent cation, lanthanum, but not by magnesium or calcium. Although the rate of pentobarbital absorption is slowed, the total amount of ¹⁴C-pentobarbital absorbed, as measured by urinary excretion, is unaltered. An antacid containing both magnesium and aluminum hydroxides retards sodium pentobarbital absorption, lowering blood and brain levels of the hypnotic and delaying its pharmacologic effect.