Interaction Between Erythromycin and Cyclosporine in a Kidney and Pancreas Allograft Recipient

Nk, Wadhwa; Tj, Schroeder; O’Flaherty, Ellen J.; Aj, Pesce; Sa, Myre; Munda, Rino; Mr, First

doi:10.1097/00007691-198703000-00022

Cited by 32 publications

(8 citation statements)

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“…As the therapeutic index of CyA is narrow, such an interaction may predispose the patient to increased toxicity. Several workers (Gonwa et al, 1986;Martell et al, 1986;Wadhwa et al, 1987a) have subsequently confirmed the interaction. In most of these reported studies, CyA was administered orally only.…”

Section: Introductionmentioning

confidence: 91%

Cyclosporin‐erythromycin interaction in renal transplant patients.

Gupta

Bakran

Johnson

et al. 1989

Brit J Clinical Pharma

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1 The interaction between cyclosporin (CyA) and erythromycin was studied in renal transplant patients following oral and intravenous administration of CyA. 2 Blood and plasma CyA concentrations and blood concentrations of metabolite 17 were measured by h.p.l.c. 3 Erythromycin produced almost a two-fold increase in bioavailability, from 36% to 60%; with a small (13%) decrease in clearance of CyA. 4 The metabolite 17 data further support the postulate that erythromycin increases the absorption of CyA rather than inhibits its metabolism, as generally believed.

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Section: Introductionmentioning

confidence: 91%

Cyclosporin‐erythromycin interaction in renal transplant patients.

Gupta

Bakran

Johnson

et al. 1989

Brit J Clinical Pharma

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“…One such drug is erythromycin. We (Freeman et al, 1987a) and others (Ptachcinski et al, 1985;Hourmant et al, 1986;Martell et al, 1986;Gonwa et al, 1986;Wadhwa et al, 1987) have previously observed that coadministration of oral CsA and erythromycin in man causes CsA concentrations to increase dramatically. Whether this effect is due to decreased hepatic metabolism or increased absorption is not clear (Freeman et al, 1987a;Gupta et al, 1988).…”

Section: Introductionmentioning

confidence: 87%

The cyclosporin‐erythromycin interaction: impaired first pass metabolism in the pig

Freeman

Grant

Carruthers

1991

British J Pharmacology

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The pharmacokinetic interaction between cyclosporin (CsA) and erythromycin has been studied in the weanling pig model. Blood CsA and metabolite‐1 (M1) concentrations were monitored by high performance liquid chromatography in portal, hepatic and jugular venus blood before and after treatment with erythromycin stearate for 7 days. Erythromycin significantly increased maximum concentration (Cmax) and area under the concentration‐time curve from 0 to 24 h (AUC) of CsA in the peripheral circulation. This was accompanied by a significant reduction in the hepatic extraction ratio calculated from portal and hepatic Cmax and AUC data. The extraction ratio appears to be concentration‐dependent in that values derived from Cmax (high concentrations) were greater than those from AUC (average concentrations). Time to Cmax (tmax) and t1/2 of CsA were essentially unchanged and no significant changes were observed in peripheral M1 kinetics apart from a small increase in tmax. The pharmacokinetic changes observed in the pig suggest that the CsA‐erythromycin interaction is caused by inhibition of hepatic metabolism and the impact of inhibition is greatest during first‐pass when CsA concentrations are at their highest.

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“…Another factor that confounds the management of cyclosporin-treated patients is the narrow range of cyclosporin blood concentrations that are both therapeutic and nontoxic.l 66 ] Erythromycin has consistently been associated with elevated cyclosporin blood concentrations and area under the plasma concentration time-curve (AUC) [68][69][70][71][72][73] and decreased cyclosporin clearance,l74,75) Interactions with cyclosporin have been observed with intravenous [69,[75][76][77][78] and oral [71 ,79-84) erythromycin, and an oral erythromycin dosage as low as 500 mg/day has been associated with a 5fold increase in trough cyclosporin concentrations. The unique pharmacokinetics of cyclosporin serve to predispose the compound to drug interactions.l 66 ) The oral absorption of cyclosporin is poor, with a mean bioavailability of 28% in renal transplant patients.…”

Section: 2 Cyclosporinmentioning

confidence: 99%

Macrolide Antibacterials

Rosensteil¹,

Adam²

1995

Drug Safety

144

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Macrolide antibiotics can interact adversely with commonly used drugs, usually by altering metabolism due to complex formation and inhibition of cytochrome P-450 IIIA4 (CYP3A4) in the liver and enterocytes. In addition, pharmacokinetic drug interactions with macrolides can result from their antibiotic effect on microorganisms of the enteric flora, and through enhanced gastric emptying due to a motilin-like effect. Macrolides may be classified into 3 different groups according to their affinity for CYP3A4, and thus their propensity to cause pharmacokinetic drug interactions. Troleandomycin, erythromycin and its prodrugs decrease drug metabolism and may produce drug interactions (group 1). Others, including clarithromycin, flurithromycin, midecamycin, midecamycin acetate (miocamycin; ponsinomycin), josamycin and roxithromycin (group 2) rarely cause interactions. Azithromycin, dirithromycin, rikamycin and spiramycin (group 3) do not inactivate CYP3A4 and do not engender these adverse effects. Drug interactions with carbamazepine, cyclosporin, terfenadine, astemizole and theophylline represent the most frequently encountered interactions with macrolide antibiotics. If the combination of a macrolide and one of these compounds cannot be avoided, serum concentrations of concurrently administered drugs should be monitored and patients observed for signs of toxicity. Rare interactions and those of dubious clinical importance are those with alfentanil and sufentanil, antacids and cimetidine, oral anticoagulants, bromocriptine, clozapine, oral contraceptive steroids, digoxin, disopyramide, ergot alkaloids, felodipine, glibenclamide (glyburide), levodopa/carbidopa, lovastatin, methylprednisolone, phenazone (antipyrine), phenytoin, rifabutin and rifampicin (rifampin), triazolam and midazolam, valproic acid (sodium valproate) and zidovudine.

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Interaction Between Erythromycin and Cyclosporine in a Kidney and Pancreas Allograft Recipient

Cited by 32 publications

References 0 publications

Cyclosporin‐erythromycin interaction in renal transplant patients.

Cyclosporin‐erythromycin interaction in renal transplant patients.

The cyclosporin‐erythromycin interaction: impaired first pass metabolism in the pig

Macrolide Antibacterials

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