how to use capillary blood samples in pediatric PK studies

Pharmacokinetic (PK) studies investigate the absorption and movement of drugs within the body. Since children absorb and process drugs differently than adults do, PK studies have to be done on children to determine safe and effective doses.

Such pediatric studies are fraught with concerns. Parents understandably do not wish for their children to be harmed or to suffer unnecessary pain because of the study itself.

PK studies used to require large volumes of blood, obtained by drawing blood from a vein. Veins can be very hard to find in children and multiple sticks may be required, causing significant pain and emotional trauma for both the child and the parents. If a large blood volume is needed, the child can incur a risk of anemia.

To avoid these problems, a technique called dried blood spotting (DBS) was developed in 1963 for use in, among other things, detecting genetic disorders in newborns. This innovation introduced the concept of microsampling. However, the hematocrit in the blood in DBS testing affects the amount absorbed and therefore the amount of drugs within that blood in PK studies. This can skew results.

Volumetric absorptive microsampling (VAMS) is a recently developed alternative technique. Instead of absorbing the capillary blood sample onto filter paper, as with traditional DBS methods, VAMS uses an absorbent tip on a sample handler. The tip is dipped into whole blood (or plasma, urine, saliva, etc.) and absorbs an exact volume, between 5 and 30 microliters. This precision eliminates the problem of hematocrit bias, as demonstrated in several studies. The tips are dried and can be stored at room temperature up to 90 days.

In the above-cited study, 200 microliters of a stable isotopically labeled soluble protein is added and the sample is placed in a shaker for 60 minutes. The tips are discarded. Centrifugation is not required in the VAMS method, saving process steps and time. A supernatant liquid is then added and the sample analyzed on the mass spectrometer for the drug levels.

As in animal studies, the use of microsampling with capillary blood samples saves time and money during the studies as well as decreasing pain and anxiety in children and their parents. In the world of pediatric PK studies, less is better.