Erythromycin Alfentanil

The enzyme is the principal participant in N-demethylation reactions where the substrate is a tertiary amine. The list of substrates includes erythromycin, ethylmor-phine, lidocaine, diltiazem, tamoxifen, toremifene, verapamil, cocaine, amiodarone, alfentanil and terfenadine. Carbon atoms in the allylic and benzylic positions, such as those present in quinidine, steroids and cyclosporin A, are also particularly prone to oxidation by CYP3A4, a range of substrates is illustrated in Figure 7.10. 

Erythromycin Drugs that may be affected by erythromycin include alfentanil, anticoagulants, benzodiazepines, buspirone, carbamazepine, cisapride, cyclosporine, digoxin, disopyramide, ergot alkaloids, felodipine, fluoroquinolones, HMG-CoA reductase inhibitors, lincosamides, methylprednisolone, penicillins, and theophyllines. Drugs that may affect erythromycin include antacids, pimozide, rifamycins, and theophyllines. 

The biotransformation of the phenylpiperidines is primarily by hepatic phase I metabolism, catalysed by cytochrome P-450 isoenzymes. The elimination of alfentanil is significantly slowed in patients treated with erythromycin, a P-450 inhibitor, with delayed recovery and prolonged postoperative respiratory depression (Bartkowski and McDonnell 1990). Apart from pethidine and phenoperidine, none of the phenylpiperidines has pharmacologically active metabolites. 

Bartkowski RR, McDonnell TE. Prolonged alfentanil effect following erythromycin administration. Anesthesiology 1990-, 73 566-8. 

A4 Acetaminophen, alfentanil, amiodarone, astemizole, cocaine, cortisol, cyclosporine, dapsone, diazepam, dihydroergotamine, dihydropyridines, diltiazem, ethinyl estradiol, gestodene, indinavir, lidocaine, lovastatin, macrolides, methadone, miconazole, midazolam, mifepristone (RU 486), paclitaxel, progesterone, quinidine, rapamycin, ritonavir, saquinavir, spironolactone, sulfamethoxazole, sufentanil, tacrolimus, tamoxifen, terfenadine, testosterone, tetrahydro-cannabinol, triazolam, troleandomycin, verapamil Barbiturates, carbamazepine, macrolides, glucocorticoids, pioglitazone, phenytoin, rifampin Erythromycin, 613-hydroxy cortisol... 

Krivoruk Y, Kinirons MT, Wood AJJ, et al. Metabolism of cytochrome P4503A substrates in vivo administered by the same route lack of correlation between alfentanil clearance and erythromycin breath test. Cbn Pharmacol Ther 1994 56 6084)14. 

Bartkowski P, Goldberg M, Larijani G, et al. Inhibition of alfentanil metabolism by erythromycin. Clin Pharmacol Ther 1989 46 99-102. 

OPIOIDS MACROLIDES Effects of alfentanil t by eiythromycin Erythromycin inhibits metabolism of alfentanil Be aware that the effects of alfentanil (especially when given as an infusion) may be prolonged by eiythromycin... 

Diltiazem reduces the elimination of alfentanil and prolongs the time to tracheal extubation (SEDA-21, 86) erythromycin may do the same (14). 

Benzodiazepines alprazolam, clonazepam, diazepam, midazolam, triazolam, zolpidem Calcium channel blockers diltiazem, nifedipine, nimodipine, verapamil Steroids androgens, estrogens, cortisol Others erythromycin, terfenadine, cyclosporine, dapsone, ketoconazole, lovastatin, lidocaine, alfentanil, amiodarone, astemizole, codeine, sildenafil... 

The CYP3A4 isozyme is responsible for the metabolism of a large number of endogenous compounds as well as a wide range of drugs (50). Fentanyl, alfentanil, and sufentanil are substrates for CYP3A4, and therefore drugs that inhibit this enzyme, such as erythromycin, HIV protease inhibitors, or cimetidine. 

CYP3A4 Alfentanil Alprazolam Astern izole Carbamazepine Cisapride Cyclosporine Diltiazem Erythromycin Felodipine Fluconazole Itraconazole Ketoconazole Lidocaine Lova statin Midazolam Nifedipine Quinidine Simvastatin Tacrolimus Terfenadine Verapamil... 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

Some patients may experience prolonged and increased alfentanil effects if they are given erythromycin or particularly troleandomycin. Troleandomycin also interacts with fentanyl but to a lesser extent Erythromycin appears not to interact with sufen-tanit... 

Erythromycin 500 mg twice daily for 7 days increased the mean half-life of alfentanil in 6 subjects from 84 to 131 minutes and deereased the clear-anee by 26%. The two most sensitive subjeets had eonsiderable changes with only one day of erythromyein treatment, and overall showed a marked change. The other4 subjeets had only small or moderate changes. ... 

A 32-year old man undergoing exploratory laparotomy was given erythromycin 1 g and neomycin 1 g, both three times daily, on the day before surgery. During the induction and maintenance of anaesthesia he received a total of 20.9 mg of alfentanil. An hour after recovery he was found to be unrousable and with a respiratory rate of only 5 breaths per minute. He was successfully treated with naloxone. Another patient given alfentanil and erythromycin is said to have developed respiratory arrest during recovery. ... 

In contrast, in 6 healthy subjeets erythromycin 500 mg twice daily for 7 days did not to affect the pharmaeokinetics of intravenous sufentanil 3 micrograms/kg in the 9 hours following administration. Two of the subjects were the same as those who had shown an alfentanil/erythromy-cin interaction cited above. 

Bartlrow RR, McDoimell TE. Piolon d alfentanil effect foUowii erythromycin administration Am esiology (1990) 73,566-8. 

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