Lack of clinically important interaction between erythromycin and theophylline

Hildebrandt, R.; Gundert‐Remy, Ursula; Möller, H.; Weber, E.

doi:10.1007/bf00542146

Cited by 12 publications

(1 citation statement)

References 13 publications

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“…After discontinuation of erythromycin she was able to resume her routine bronchodilator therapy. A recent study by Hildebrandt et al (1984) in 11 volunteers found that the kinetics of theophylline and its metabolites were unchanged by administration of erythromycin stearate 250mg 4 times daily for 10 days. Theophylline was administered as a 280mg intravenous bolus followed by a constant rate infusion (23.8 ± 4.1 mg/h) for 6 hours before and after the 10-day erythromycin administration.…”

Section: Erythromycinmentioning

confidence: 96%

Pharmacokinetic Interactions of the Macrolide Antibiotics

Ludden

1985

Clinical Pharmacokinetics

134

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The macrolide antibiotics erythromycin and triacetyloleandomycin (troleandomycin) are prescribed for many types of infections. As such they are often added to other preexisting drug therapy. Thus, there are frequent opportunities for the interaction of these antibiotics with other drugs. Both erythromycin and triacetyloleandomycin appear to have the potential to inhibit drug metabolism in the liver and also drug metabolism by micro-organisms in the gut, either through their antibiotic effect or through complex formation and inactivation of microsomal drug oxidising enzymes. Of the two agents, triacetyloleandomycin appears to be the more potent inhibitor of microsomal drug metabolism. Published studies indicate that triacetyloleandomycin can significantly decrease the metabolism of methylprednisolone, theophylline and carbamazepine. Its ability to cause ergotism in patients receiving ergot alkaloids and cholestatic jaundice in patients on oral contraceptives may also be related to its inhibitory effect on drug metabolism. Erythromycin appears to be a much weaker inhibitor of drug metabolism. There are numerous reports describing apparent interactions of erythromycin with theophylline and a lesser number of reports dealing with carbamazepine, warfarin methylprednisolone and digoxin. There are sufficient data to suggest that erythromycin can, in some individuals, inhibit the elimination of methylprednisolone, theophylline, carbamazepine and warfarin. The mean change in drug clearance is about 20 to 25% in most cases, with some patients having a much larger change than others. Like tetracycline, erythromycin also appears to have the potential for increasing the bioavailability of digoxin in patients who excrete high amounts of reduced digoxin metabolites, apparently through destruction of the gut flora that form these compounds. Concurrent administration of triacetyloleandomycin with drugs whose metabolism is known to be affected or that could potentially be affected should be avoided unless appropriate adjustments in dosage are made. Coadministration of erythromycin with drugs believed to interact should be undertaken with caution and with appropriate patient monitoring. Among the other macrolide antibiotics, josamycin has seldom been involved in causing drug interactions, while midecamycin and the older derivative spiramycin have not so far been incriminated.

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Section: Erythromycinmentioning

confidence: 96%

Pharmacokinetic Interactions of the Macrolide Antibiotics

Ludden

1985

Clinical Pharmacokinetics

134

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Cyclosporin A and erythromycin: A study of a drug interaction in the in situ perfused rat liver model

Hughes¹,

Swanton

Collier³

1993

Biopharm & Drug Disp

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Using the in situ perfused rat liver model, the effect of erythromycin (Ery) on the disposition of cyclosporin A (CyA) and the major human metabolite, AM1, was investigated. Prior to perfusion experiments, oral dosing was carried out for three days on three groups of male Sprague-Dawley rats (300-350 g), involving pretreatment with water (control and H2O/Ery groups) or erythromycin (Ery oral group). On the fourth day, perfusion experiments took place using standard techniques, with the addition of 20 mg Ery to the H2O/Ery and Ery oral groups, and 2.5 mg CyA to all groups. Perfusate and bile samples were collected and assayed for CyA and AM1 by HPLC. Results indicated that inhibition of CyA metabolism had occurred as the CyA concentration in perfusate was significantly higher in both Ery groups at all times compared to the control group, and the levels of AM1 in both perfusate and bile were significantly lower than in the control group. There was also a marked reduction in the apparent metabolic clearance of CyA in the Ery groups. It was concluded that AM1 production had been inhibited by Ery, the most likely mechanism being inhibition of the isoenzyme CYP3A with which Ery forms a stable complex.

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Effect of miocamycin on theophylline kinetics in children

Principi

Onorato

Giuliani

et al. 1987

Eur J Clin Pharmacol

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The interaction between a new macrolide antibiotic, miocamycin, and theophylline was evaluated in a single cross-over study in 5 asthmatic children. Each patient received a single dose of theophylline (4.3 mg/kg) delivered in 15 min using a constant-rate infusion pump, immediately before and after a 10 day course of miocamycin 17.5 mg/kg b.d. The pharmacokinetics of theophylline were calculated for each phase of the study. The elimination rate constant (3.92 vs 3.74 h-1), the mean total body clearance (1.71 vs 1.8 ml X min X kg-1) and the mean apparent volume of distribution (0.57 vs 0.581 X kg-1) did not differ. The result can be explained by the inability of the antibiotic to form inactive cytochrome P-450 metabolite complexes which can interfere with the metabolism of theophylline. Thus, miocamycin can safely be administered to asthmatic children requiring theophylline treatment, when they have an infection due to susceptible pathogens.

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Lack of clinically important interaction between erythromycin and theophylline

Cited by 12 publications

References 13 publications

Pharmacokinetic Interactions of the Macrolide Antibiotics

Pharmacokinetic Interactions of the Macrolide Antibiotics

Cyclosporin A and erythromycin: A study of a drug interaction in the in situ perfused rat liver model

Effect of miocamycin on theophylline kinetics in children

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