The interaction of erythromycin with theophylline

Abstract

We have studied the interaction of erythromycin with theophylline. We gave ten healthy volunteers theophylline as an intravenous loading dose (5 mg X kg-1) over 1 h, followed by a maintenance infusion (0.5 mg X kg-1 X h-1) for 5 h. A second infusion of theophylline was given after 9 days of treatment with 1 g erythromycin base daily, and the concentrations of theophylline were determined during the infusion periods. The concentrations of erythromycin were measured for 8 h, after one week of treatment, and also after the last erythromycin dose, simultaneously with the second theophylline infusion. Concentrations within the therapeutic range were obtained with both drugs. A significant increase in both AUC and mean plasma concentrations of theophylline was seen during erythromycin treatment. The plasma clearance of theophylline was reduced in 9 of the 10 subjects. Renal clearance increased correspondingly, but the change was not statistically significant. Serum concentrations of erythromycin fell significantly, by more than 30%, with concurrent theophylline medication. We conclude that an interaction between theophylline and erythromycin, affecting both drugs, can be shown with concentrations of the drugs within the therapeutic range.

Effect of the Treatment Period With Erythromycin on Cytochrome P450 3A Activity in Humans

“…Many studies have shown that pretreatment with erythromycin produces significant increases in plasma concentrations of clinically important drugs such as immune modulators, 7 HIV antivirals, 8 theophylline, 9 , 10 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors, 11 and benzodiazepines 12 , 13 . However, these studies were performed with varied treatment periods of 2 to 10 days of erythromycin, which may affect the extent of drug interactions via CYP3A inhibition.…”

Gauging Reactive Metabolites in Drug-Induced Toxicity

“…Numerous compounds that form MI complexes with CYP3A4 have been shown to cause clinically significant drug-drug interactions, e.g. erythromycin [182][183][184][185][186][187], nicardipine [188][189][190], and troleandomycin [177,191,192]. Erythromycin is a weak inhibitor of CYP3A4, but during the N-demethylation of erythromycin, a nitroso intermediate is formed which ligates the heme iron and forms a stable complex which prevents further catalysis by the enzyme.…”

Adverse drug interactions in dentistry

“…The end result of this type of interaction is a diminished biotransformation of the substrate drug leading to an exaggerated pharmacological effect resembling an overdose of the substrate drug, unless the substrate drug is a prodrug. For example, the ability of erythromycin (an enzyme inhibitor) to reduce the metabolism of theophylline (a drug substrate) can lead to dysrhythmias, tremors, and seizures (189). In the presence of enzyme inhibitors, the toxicities resulting from these types of interactions have contributed to the removal of several widely marketed substrate drugs from the U.S. marketplace, including the cholesterol-lowering drug cerivastatin because of an unusually high incidence of rhabdomyolysis, and both the non-sedating antihistamines astemizole and terfenadine and the gastroesophageal reflux drug cisapride for a number of reports of life-threatening ventricular arrhythmias known as torsades de pointes ( Table 2) (118).…”

“…Excessive blood levels of tacrine induced by concomitant erythromycin or ciprofloxacin therapy could thus be manifested in excessive cholinergic activity at both muscarinic and nicotinic cholinergic receptors, possibly resulting in excessive salivation, lacrimation and sweating, gastrointestinal hypermotility, bradycardia, pupillary constriction, muscle cramps, and central nervous system excitation/agitation (29). Table 3 lists the potential clinical outcomes of coadministration of erythromycin or ciprofloxacin with some CYP1A2 substrates (24, 29, 189, 195, 221, 227, 231, 247).…”