Source: Health Products Regulatory Authority (IE) Revision Year: 2013 Publisher: Aspen Pharma Trading Limited 3016 Lake Drive Citywest Business Campus Dublin 24 Ireland
ATC code: L0JBB03
Tioguanine is a sulphydryl analogue of guanine and behaves as a purine antimetabolite. It is activated to its nucleotide, thioguanylic acid.
Tioguanine metabolites inhibit de novo purine synthesis and purine nucleotide interconversions. tioguanine is also incorporated into nucleic acids and DNA (deoxyribonucleic acid) incorporation is claimed to contribute to the agent’s cytotoxicity. Cross-resistance usually exists between tioguanine and mercaptopurine, and it is not to be expected that patients resistant to one will respond to the other.
Tioguanine is extensively metabolised in vivo. There are two principal catabolic routes: methylation to 2-amino-6- methyl-thiopurine and deamination to 2-hydroxy-6-mercaptopurine, followed by oxidation to 6-thiouric acid.
Studies with radioactive tioguanine show that peak blood levels of total radioactivity are achieved about 8-10 hours after oral administration and decline slowly thereafter. Later studies using HPLC have shown 6-tioguanine to be the major thiopurine present for at least the first 8 hours after intravenous administration. Peak plasma concentrations of 61 – 118 nanomol (nmol)/ml are obtainable following intravenous administration of 1 to 1.2g of 6-tioguanine/ m² body surface area.
Plasma levels decay biexponentially with initial and terminal half-lives of 3 and 5-9 hours respectively. Following oral administration of 100mg/m², peak levels as measured by HPLC occur at 2-4 hours and lie in the range of 0.03-0.94 micromolar (0.03-0.94 nmol/ml). Levels are reduced by concurrent food intake (as well as vomiting).
Tioguanine has been shown to be carcinogenic in animals. The theoretical possibility of a similar effect should be borne in mind when designing the long-term management of the patient.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
