Pharmacokinetic Studies in Infants Using Minimal-Risk Study Designs
Daniel K. Benjamin Jr.,
P. Brian Smith,
Kevin M. Watt.
Infants are therapeutic orphans. Many drugs used in infants are used “off-label”, increasing the risk of drug
toxicity and suboptimal efficacy in this vulnerable population. This knowledge gap in clinical pharmacology is partly
attributed to challenges associated with conducting clinical trials in infants. Consequently, there is a need for novel and
efficient study designs more suited to this population. Available literature describing the use of minimal-risk approaches
to characterize the pharmacokinetics (PK) of drugs in infants was critically reviewed. Population PK approach with sparse
sampling was found to be well established. Other, more recent alternatives, like dried blood spots sampling, opportunistic
design, and the use of non-blood matrices are promising strategies with an increasing number of applications in infants.
Physiologically based pharmacokinetic modeling provides valuable insight in drug disposition but still needs more
prospective validation. Increasing experience with these methods provides understanding of their strengths and limitations
and will help improve the design of future PK studies in infants.
Keywords: Clinical trial, dried blood spots, infants, pharmacokinetics, population pharmacokinetics, scavenged sampling,
sparse sampling, ultra–low-volume drug assays.
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