6-Mercaptopurine: Oral administration and i.v. bolus injections in dogs

Abstract

6-Mercaptopurine (6MP) levels in serum of dogs were studied after long-term oral administration and intravenous injection. During long-term daily oral administration of 50 mg of 6MP, more or less constant levels of 6MP have been found after 1–3 weeks. After stopping administration of the drug, 6MP concentrations remained constant for a further period of 3–6 weeks and then declined within 1–2 weeks below the limit of detection. I.v. bolus injections of 50 mg of 6MP resulted in concentration v. time curves which fitted into an open two-compartment pharmacokinetic model. Half-life times were in a range of 13–21 and 125–151 min, respectively. Peak concentrations were from 2,500 to 10,500 nmol/l. Our data on i.v. push injections with a customary clinical dose revealed peak concentrations which were low in comparison to the concentrations used in in vitro studies by Tidd and Paterson to achieve maximal cell-kill. Moreover, the half-life times of the 6MP after i.v. bolus injections are short, so prolonged high plasma concentrations are not obtained by i.v. bolus injections. We suggest that prolonged infusions of 6MP at relatively high dose rates should result in higher and persisting plasma concentrations and so should promise a more potent antitumour activity.

Key Words:

• 6-Mercaptopurine