Systemic exposure to mercaptopurine as a prognostic factor in acute lymphocytic leukemia in children

Article Abstract:

Disease remission in children with acute lymphocytic leukemia (a type of leukemia characterized by immature, incompetent white blood cells) can now be achieved in more than 90 percent of all cases, but between 30 and 40 percent of patients relapse. During remission, children usually receive oral mercaptopurine and methotrexate (maintenance therapy), yet they can experience a relapse in spite of this drug regimen. It is possible that bioavailability (the amount of ingested drug actually available to the body) varies, so that children who receive similar doses are not, in fact, exposed to the same amount of therapeutic agent. This was tested by evaluating 23 children diagnosed as having acute lymphocytic leukemia during maintenance therapy. Patients were classified as being at low or standard risk of relapse according to accepted criteria. Mercaptopurine concentrations in blood samples were analyzed at regular intervals, as were white blood cell counts. Relapse occurred in 3 of the 11 low-risk, and 7 of the 12 standard-risk, patients. There were no differences between children who relapsed, and those who did not, in terms of age, white-cell count during maintenance therapy, dose of mercaptopurine or methotrexate, or other related variables. However, significant differences were found between the two groups in the area under the concentration-time curve (a graphic indicator of the amount of drug available at different times after administration), which was greater for children who did not relapse. Systemic exposure (the amount of drug to which the body was actually exposed) to mercaptopurine during the first 100 days of the study was also greater for these children than for those who relapsed. These differences were found when low- and standard-risk patients were evaluated separately. The results show that differences between children in their abilities to metabolize chemotherapeutic drugs may be important in determining the effects these drugs have. On the average, children who relapsed had only two thirds of the area under the concentration-time curve that nonrelapsing patients had. Doses of maintenance therapy should be calculated to provide optimal systemic exposure, not simply the amount required by the therapeutic protocol. (Consumer Summary produced by Reliance Medical Information, Inc.)

Prognosis, Drug therapy, Acute lymphocytic leukemia, Childhood leukemia, Mercaptopurine, Lymphocytic leukemia in children

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Determination of gestational cocaine exposure by hair analysis

Article Abstract:

Blood and urine tests are only capable of detecting recent cocaine use. Since cocaine is deposited in the hair, a method was tested for its ability to detect past cocaine use from analysis of hair. The levels of benzoylecgonine, a product of cocaine breakdown, were measured in the hair of 16 adults whose urine tests were negative for cocaine. The levels of the cocaine metabolite were higher in heavy cocaine users than in occasional users. Although cocaine was detected in the hair of newborns whose mothers used cocaine, the drug could not be detected in the hair of infants of one year and older because they had lost their fetal hair. The detection of cocaine by hair analysis may prove to be beneficial in determining prenatal exposure to cocaine when the maternal drug history is either unavailable or dubious. This test may also prove to be helpful in studies of reproductive risks of cocaine because it can accurately identify exposed and nonexposed populations in certain age groups.

Cocaine abuse

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Drug screening in unconventional matrix: hair analysis

Article Abstract:

The problems associated with drug screening by hair analysis are discussed. Since drugs require time to deposit into the hair, drug exposure shortly before birth will not be detected in newborn hair, and urine analysis may be more useful for drug screening. Drugs are deposited in the hair in very small amounts, and hair samples taken for testing tend to be very small, particularly from newborns. Consequently the techniques for drug testing by hair analysis must be very sensitive. Current methods tend to be complex and not routinely available in clinical laboratories. Because hair is one of the most exposed parts of the body, its composition may be altered by agents in the environment, such as hair spray or automobile exhaust fumes. Drug screening by hair analysis must be analyzed with caution.

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