Pharmacokinetics of mercaptopurine

The anatomical distribution of mercaptopurine was investigated in rats at dose levels of 2.5 and 25 mg/kg iv. The plasma and tissues were analyzed by radioisotopic dilution and spectrofluorometric techniques. The tissue-plasma ratios were: liver-plasma, approximately 4.0; kidney-plasma, approximately 2.4; spleen-plasma, approximately 1.7; muscle-plasma, approximately 1.4; gut lumen-plasma, approximately 3; and bone marrow-plasma, approximately 0.35. Physiologically based pharmacokinetic models were developed to simulate concentrations of mercaptopurine in plasma, kidneys, liver, muscle, spleen, bone marrow, and gut lumen. The agreement between experimental and predicted plasma and tissue profiles was good. Human plasma levels of mercapto-purine were predicted and, when compared with clinical data, demonstrated reasonable agreement.