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Pharmacokinetics of 6-mercaptopurine (6MP) in the monkey. I. Disposition from plasma and cerebrospinal fluid following iv bolus.

The disposition profile of 6-mercaptopurine (6MP) was studied from plasma and cerebrospinal fluid (CSF) in the rhesus monkey following a single iv bolus dose (4 mg/kg). A new, sensitive, and specific high performance liquid chromatography procedure has been employed for drug quantitation in biological fluids. An equation consisting of three exponential terms was simultaneously fitted to the 6MP plasma and CSF concentration vs. time data using the SAAM 27 digital computer program. 6MP in plasma and CSF had a mean half-life (t1/2, lambda z) of 2.9 hr and an apparent volume of distribution (Vd, lambda z) of 3.00 liter/kg. Estimates of total body clearance average 0.731 +/- 0.412 liter/hr/kg and ranged between 0.446 and .1204 liter/hr/kg. In the postdistributive phase, the decline of 6MP concentration from the CSF paralleled plasma. The t1/2, lambda z obtained by fitting Ccsf vs. t data separately was not significantly different (p greater than 0.2) than the one obtained above in a simultaneous fitting of the data. Therefore, it appears that the unbound 6MP concentration in plasma may be the driving force in the diffusion of the drug into CSF. Comparison of experimental CSF/plasma ratio of 6MP with the theoretical values obtained using the pH-partition hypothesis is also discussed.