We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Article |

Diurnal Variation in the Pharmacokinetics and Myelotoxicity of Mercaptopurine in Children With Acute Lymphocytic Leukemia

Gideon Koren, MD; Anne Marie Langevin, MD; Nancy Olivieri, MD; Ester Giesbrecht, MSc; Alvin Zipursky, MD; Mark Greenberg, MD
Am J Dis Child. 1990;144(10):1135-1137. doi:10.1001/archpedi.1990.02150340081028.
Text Size: A A A
Published online


• During their maintenance therapy, children with acute lymphoblastic leukemia are treated with a daily dose of mercaptopurine for several years. A recent retrospective analysis has suggested that administration of the drug in the evening results in a better prognosis. We compared the disposition pharmacokinetics of mercaptopurine administered in the morning vs in the evening in 13 children with acute lymphoblastic leukemia. Elimination half-life of mercaptopurine was significantly longer in the evening than during the day (423 ±142 minutes vs 176 ± 22 minutes, mean ± SEM). The area under the concentration-time curve (AUC0-∞) was significantly larger in the evening (24713±3536 ng/mL per minute vs 17120±1474 ng/mL per minute). These differences were even more pronounced when comparing the area under the curve of the postdistributive phase (AUC300 mln.−∝ 7724 ± 2955 ng/mL per minute in the evening vs 2597 ± 712 ng/mL per minute during the day). In a second study, 12 children with acute lymphoblastic leukemia receiving mercaptopurine in the morning had their medication administration switched to the evening. Within 2 weeks there was a sharp fall in peripheral white blood cell counts in all patients (from 4.1 109/L to 2.2 - 109/L) mainly due to a drop in polymorphonuclear lymphocytes (from 2.78×109/L to 1.05×109/L). We conclude that the diurnal variations of mercaptopurine disposition result in clinically important myelotoxicity of the drug.

(AJDC. 1990;144:1135-1137)


Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?





Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.