Enhancement by sodium salicylate of the blood glucose lowering effect of chlorpropamide‐drug interaction or summation of similar effects?

Abstract

1 The ability of sodium salicylate (3 g) to enhance the blood glucose lowering action of chlorpropamide (200 mg) has been confirmed in healthy male volunteers who received an oral test dose of 50 g glucose. Salicylate raised the plasma concentration of insulin and lowered that of cortisol but did not alter the concentration of chlorpropamide. 2 The area under the blood glucose concentration-time curve was used as the measure of drug response and the significance of drug effects was assessed by analysis of variance. In one study on five volunteers the effect of combining salicylate and chlorpropamide was additive. In a second study on six volunteers 200 mg chlorpropamide, 3 g sodium salicylate and 100 mg chlorpropamide + 1.5 g salicylate were equi-effective. 3 The enhancement of chlorpropamide action by salicylate in this single dose study is consistent with the summation of similar effects. It is not necessary to postulate an interaction.

Clinical Pharmacology of Sulfonylureas

“…Similarly no pharmacokinetic interactions have been reported for lovastatin, salicylate, cimetidine and enoxacin RICHARDSON et al 1986;SHAH et al 1985;LOGEMANN 1986). Activated charcoal can reduce the absorption (NEUVONEN and KÄRKÄINEN 1983) and chloramphenicol, sulfaphenazole, bishydroxycoumarin or phenylbutazone may inhibit chlorpropamide metabolism (DALGAS et al 1965;KRISTENSEN and HANsEN 1968;PETITPIERRE et al 1972).…”

Drug Metabolism

“…In contrast, no comparable changes have been noticed in the biotansformation of acetaminophen to its sulphate conjugate. Also, no changes in the plasma glucuronide/oxazepam ratio were observed, suggesting a substrate specificity of the inductive effect exerted by cabbage or Brussels sprout [125].…”

“…However, some activity has also been detected in microsomes, cytosol and even in the extracellular space. Its presence in the brain is of particular importance in connection with the therapeutic profile of its inhibitors and its role as an activator of xenobiotics [121][122][123][124][125][126].…”

Adverse Drug Interactions with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

“…While the mechanism for this interaction is unDrug Safety 8 (2) 1993 known, it may be due to a summation of similar effects since large doses of salicylates (1.5 to 3g) are hypoglycaemic in the absence of a sulphonylurea agent (Giugliano & D'Onofrio 1980;Richardson et al 1986). However, salicylates may be administered to patients receiving sulphonylureas safely provided blood sugar levels are monitored closely.…”