Medicines Ketoconazole

A major breakthrough in modern medicine has been the discovery of effective anti-fungal compounds. One family such as ketoconazole 204 or saperconazole 205 has a dioxolan core carrying the active imidazole or triazole functionality. Schering-Plough have developed a new type having an apparently simpler tetrahydrofuran (THF) core such as 206. This compound presents special problems for asymmetric synthesis. 

Ketoconazole and tioconazole are currently prescription-only medicines, but qualified podiatrists registered with the Health Professions Council are able to access and supply tioconazole 28% (as from November 2006). 

Ketoconazole is not available on the NHS for tinea infections, but tubes of maximum 15 g ketoconazole 2% can be sold over the counter and as such could be supplied by registered podiatrists. See Chapter 14 for more information on how the law applies to sale and supply of medicines by podiatrists. 

An active substance, although initially released from its dosage form (and dissolved), may become unavailable for absorption due to reactimis with other medicines or food components [4]. An example is the formation of insoluble complexes of tetracycline with calcium or aluminium ions from antacids or milk products. Interaction (chelation or binding) with iron ions leads to a reduced absorption for a variety of active substances such as doxycycline, penicillamine, methyldopa and ciprofloxacin. The absorption of active substances showing pH-dependent dissolution behaviour may be influenced by medicines that influence the gastric pH, such as H2-antagonists, proton pump inhibitors and antacids. Antimycotic active substances such as ketoconazole or itraconazole dissolve better in acidic fluids. Therefore their bioavailability may be increased by the concomitant use of an acidic drink like cola, whereas the concomitant use of antacids or proton pump inhibitors is likely to reduce the bioavailability. Concomitant use of milk may increase the dissolution of acidic active substances, whereas fats from food may increase the bioavailability of lipophilic active substances like albendazole and griseofulvin. 

---