DRUG ABSORPTION IN RATS PRETREATED WITH ANTIBIOTICS

¹ Department of Pharmacology and Experimental Therapeutics, Boston University Medical Center, Boston, Massachusetts

The bacterial population of the small intestine has been shown to influence the absorption of a variety of dietary substances. This study was undertaken to determine whether alterations of the bacterial population produced by antibiotics might affect the intestinal absorption of pharmacologic agents. After a treatment period during which antibiotics were administered to rats in their drinking water, assays were performed to measure the ileal bacterial population and the ileal absorption of a series of drugs. A mean 10-day consumption of 100 mg/kg/day of neomycin sulfate and 24 mg/kg/day of potassium penicillin V produced a marked reduction in the counts of coliforms and proteus, enterococci, lactobacilli and anaerobic lactobacilli and streptococci. No significant differences between control and pretreated animals were found, however, in the absorption of tetracycline, diphenylhydantoin or benzomethamine. A regimen of lincomycin, averaging 61 mg/kg/day for 7 days, eliminated the lactobacilli population and produced overgrowths in coliforms in two out of three experiments. The ileal absorption of benzomethamine and chlorpromazine was not affected by this antibiotic pretreatment. Three regimens of tetracycline, averaging 110 mg/kg/day for 2 days, 209 mg/kg/day for 2 days and 33S mg/kg/day for 5 days, all produced small reductions in anaerobic lactobacilli and streptococci. No differences were observed in the absorption of chlorpromazine as a result of tetracycline pretreatment. These antibiotic regimens that altered the enteric bacterial population apparently do not produce changes that are significant to the absorption process of the drugs that were studied.