Clinical pharmacologic observations on 6-mercaptopurine and 6-methylthiopurine ribonucleoside.

Abstract

Gastrointestinal absorption of 6‐mercaptopurine (MP) was incomplete and variable. After a single intravenous iniection, its plasma half‐life was 21 minutes in children and 47 minutes in adults. However, in 6 hours the cumulative urinary excretion of MP in each was about 20 per cent of the administered dose. The passage of MP into the red blood cells and into the cerebrospinal fluid was minimal. MP was 19 per cent bound to plasma protein. In contrast, the study on 6‐methylthiopurine ribonucleoside (MMPR) showed that the highest plasma level of radioactivity in patients on MMPR‐S35 occurred at 1 to 2 days following both oral and intravenous routes. Gastrointestinal absorption was complete. The half‐life of plasma radioactivity was 5 days. Radioactivity was concentrated within human red blood cells to a 40 to 1 concentration gradient over plasma; the radioactivity was in the form of MMPR 5'‐monophosphate. This anabolite persisted in the red cells for as long as 6 weeks. Excretion of radioactivity was slow and sustained, about 10 per cent daily of the MMPR dose. Only unchanged MMPR was detected in urine during the first day; in later urine samples, principally the 5'‐monophosphate was found. MMPR was largely excluded from the cerebrospinal fluid. It was 39 per cent bound to plasma protein.