Drugs 2004; 64 (1): 63-88 REVIEW ARTICLE 0012-6667/04/0001-0063/$34.00/0 © 2004 Adis Data Information BV. All rights reserved. The Glycylcyclines A Comparative Review with the Tetracyclines George G. Zhanel, 1,2,3 Kristen Homenuik, 4 Kim Nichol, 1,3 Ayman Noreddin, 1 Lavern Vercaigne, 4,5 John Embil, 1,2 Alfred Gin, 4,5 James A. Karlowsky 6 and Daryl J. Hoban 1,3 1 Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada 2 Department of Medicine, Health Sciences Centre, Winnipeg, Manitoba, Canada 3 Clinical Microbiology, Health Sciences Centre, Winnipeg, Manitoba, Canada 4 Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada 5 Pharmacy, Health Sciences Centre, Winnipeg, Manitoba, Canada 6 Focus Technologies, Herndon, Virginia, USA Contents Abstract ..................................................................................... 64 1. Chemistry ................................................................................ 65 2. Mechanism of Action ...................................................................... 68 3. Mechanism of Resistance .................................................................. 68 4. In Vitro Activity ........................................................................... 70 5. Pharmacokinetics ......................................................................... 72 5.1 Absorption ........................................................................... 72 5.2 Distribution ........................................................................... 72 5.3 Elimination ........................................................................... 74 5.4 Pharmacodynamics .................................................................. 74 6. Trials in Animals and Clinical Trials ........................................................... 76 7. Adverse Effects ........................................................................... 83 7.1 Gastrointestinal ....................................................................... 83 7.2 Central Nervous System ............................................................... 83 7.3 Effects on Teeth and Bone ............................................................. 84 7.4 Hepatic .............................................................................. 84 7.5 Renal ................................................................................ 84 7.6 Hypersensitivity Reactions .............................................................. 84 7.7 Haematological ...................................................................... 84 7.8 Miscellaneous ........................................................................ 84 8. Drug Interactions .......................................................................... 84 8.1 Antacids, Calcium, Magnesium, Iron, Sodium Bicarbonate and Binding Resins .............. 84 8.2 Anticoagulants ....................................................................... 84 8.3 Antidiarrhoeal Agents ................................................................. 85 8.4 Anticonvulsants ....................................................................... 85 8.5 Digitalis Glycosides .................................................................... 85 8.6 Diuretics ............................................................................. 85 8.7 Insulin ................................................................................ 85 8.8 Methoxyflurane ....................................................................... 85 8.9 Oral Contraceptives .................................................................. 85 8.10 Penicillin ............................................................................ 85 9. Role of Glycylcyclines ..................................................................... 85