Hormonal Macrolides

Andrew Regan was born in Rawtenstall, Lancashire and studied at the University of Cambridge, where he obtained his BA in 1981 (MA 1985), and his PhD in 1984, under the supervision of Professor Jim Staunton. From 1984-1985 he held an SERC-NATO Research Fellowship at Columbia University in the laboratories of Professor Gilbert Stork. He returned to the UK in 1985 to a lectureship in organic chemistry at the University of Kent at Canterbury, and since 1990 has been a lecturer in the Department of Chemistry at the University of Manchester. His research interests include the synthesis of phosphinic-acid hormone mimics, simplified macrolide antibiotics and anti-tumour compounds, stereoselective methodology, and the use of enzymes in synthesis. 

Agents that may increase theophylline levels include allopurinol, beta blockers (nonselective), calcium channel blockers, cimetidine, oral contraceptives, corticosteroids, disulfiram, ephedrine, influenza virus vaccine, interferon, macrolides, mexiletine, quinolones, thiabendazole, thyroid hormones, carbamazepine, isoniazid, and loop diuretics. 

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

Schlusener MP, Bester K (2005) Determination of steroid hormones, hormone conjugates and macrolide antibiotics in influents and effluents of sewage treatment plants utilizing high-performance liquid chromatography/tandem mass spectrometry with electrospray and atmospheric pressure chemical ionization. Rapid Commun Mass Spectrom 19 3269-3278... 

Antibiotics such as tetracyclines and macrolides are the agents of choice for papulopustular acne. In severe papulopustular and nodu-locystic/conglobate acne, oral isotretinoin is the treatment of choice. Hormonal therapy represents an alternative effective regimen in female patients. 

Motilin, a 22-amino acid peptide hormone found in the GIM cells and some entervchromajfin cells of the upper small bowel, is a potent contractile agent of the upper GI tract. The effects of motilin can be mimicked by erydiromycin and by other macrolide antibiotics (see Chapter 46), including oleandomycin, azithromycin, and clarithromycin. 

The macrolides clarithromycin, dirithromycin, roxithromycin and telithromycin appear unlikely to cause combined hormonal contraceptive failure. Erythromycin is also not considered to cause failure of combined hormonal contraceptives, but isolated anecdotal cases have been reported. An isolated case has also been reported with spiramycin. 

The macrolides such as erythromycin might possibly be expected to suppress the bacteria responsible for the enterohepatic recycling of ethinylestradiol, but good evidence that this is clinically important is scant (see Hormonal contraceptives + Antibacterials Penicillins , p.981). Erythromycin, and to a lesser extent the other macrolides discussed here, also inhibit the cytochrome P450 isoenzyme CYP3A4, which is responsible for the metabolism of the contraceptive steroids. Therefore they might be expected to increase rather than reduce contraceptive efficacy. This would be expected to offset any possible reduced enterohepatic recycling. 

As a result of the design of multi-residue methods for such purposes, they are intrinsically prone to provide false positive results. A good example is provided by work designed to monitor residues of some macrolide antibiotics as well as some steroid hormones (Schliisener 2005) in unfiltered influents and effluents of sewage treatment... 

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