PEDIATRICS Vol. 50 No. 6 December 1972, pp. 954-955
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DRUG INTERACTIONS—PART IV

Interactions Among Antimicrobial and Nonantimicrobial Agents

Harris D. Riley Jr. M.D.1

1 Department of Pediatrics and Pediatric Pharmacology Unit, Children's Memorial Hospital, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma

Activity of one drug may be modified by prior or simultaneous administration of another, and improved therapy is sometimes possible by concurrent medication. However, serious adverse effects may also arise from drug interaction.1 Interactions are caused by altered absorption, distribution, biotransformation or excretion of drugs, or from adjunctive action. In this communication certain known interactions affecting antimicrobial agents will be reviewed briefly and their mechanisms noted.

Preadministration Interactions

Besides chemical actions between drugs themselves before administration, as in infusion preparations, there may also be interaction between infusion vehicle and drug, and even between a drug and the container. Tetracyclines are photoxidized by the riboflavin in vitamin B complex and become inactive and change color in alkaline solutions. Kanamycin and methicilin inactivate each other, and bisulfite inactivates penicillin G.

Postadministration—Carrier Site Displacements

Interactions may take place after drugs have been absorbed and metabolized. Most antibiotics circulate in the blood reversibly bound to serum albumin. Each albumin molecule has several binding sites and the extent of binding varies from almost none with certain drugs, such as cephaloridine, kanamycin, vancomycin, polymyxin B and colistin, to 90% or more for oxacillin, cloxacillin, dicloxacillin, demeclocycline, novobiocin, and some of the long-acting sulfonamides.2,3 The protein-bound portion is metabolically inactive, but the free portion is active. When highly bound drugs compete for the same binding site, one or both may be displaced.4,5

Clinically significant responses may result when the bound fraction of one drug is displaced from its binding site by a second drug of greater affinity.6