Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

First-time-in-human dose selection: allometric thoughts and perspectives

H Boxenbaum1, C DiLea

  • 1Wyeth-Ayerst Research, Philadelphia, Pennsylvania 19101, USA.

Journal of Clinical Pharmacology
|October 1, 1995
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Pharmacokinetic determinants in the design and evaluation of sustained-release dosage forms.

Pharmaceutical research·2013
Same author

Commentary: does caloric restriction induce hormesis?

Human & experimental toxicology·2000
Same author

Human in vivo competitive inhibition of P450 substrates: increased plasma concentrations as a function of hepatic extraction ratio and percent inhibition.

Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques·2000
Same author

Pharmacokinetics tricks and traps: drug dosage adjustment in renal failure.

Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques·2000
Same author

Cytochrome P450 3A4 in vivo ketoconazole competitive inhibition: determination of Ki and dangers associated with high clearance drugs in general.

Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques·2000
Same author

Pharmacokinetics tricks and traps: flip-flop models.

Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques·2000
Same journal

FDA Gene Therapy Approvals (1998-2025): Current Status, Regulatory Evolution, and Future Directions.

Journal of clinical pharmacology·2026
Same journal

Human Disposition, Metabolism, and Excretion of Sevasemten (EDG-5506), a Selective Modulator of Fast Myosin in Healthy Volunteers.

Journal of clinical pharmacology·2026
Same journal

New Insights into Genetic Polymorphisms Influencing the Therapeutic Efficacy and Toxicity of Rivaroxaban.

Journal of clinical pharmacology·2026
Same journal

Physiologically Based Pharmacokinetic Modeling to Predict the Pharmacokinetics of Sacubitril/Valsartan in the Elderly with Renal or Hepatic Impairment Population.

Journal of clinical pharmacology·2026
Same journal

The Journal of Clinical Pharmacology: 65 Years of History.

Journal of clinical pharmacology·2026
Same journal

Decoupling CAR-T Expansion, Conversion, and Decay Timing: Physiologically Aligned Semi-Mechanistic Modeling With Smooth Gating and a Cauchy Likelihood Residual Model.

Journal of clinical pharmacology·2026
See all related articles

Determining the first dose in human studies involves complex preclinical factors like toxicology and pharmacokinetics. Current methods lack a definitive algorithm, relying on established rules of thumb due to inherent uncertainties.

Area of Science:

  • Pharmacology and Toxicology
  • Clinical Trial Design

Background:

  • First-time-in-human (FTIH) studies require careful dose selection to ensure safety.
  • Preclinical data is crucial but presents challenges in predicting human response.

Purpose of the Study:

  • To examine factors influencing dose selection in early-phase clinical trials.
  • To discuss the limitations of current methods for determining initial human doses.

Main Methods:

  • Review of factors including animal toxicology, toxicokinetics, and allometric scaling.
  • Integration of preclinical pharmacologic and toxicologic data.
  • Discussion of pharmacokinetic and body surface area correlations.

Main Results:

  • Preclinical evaluation can mitigate risks in Phase I trials.

Related Experiment Videos

  • Significant uncertainties remain in predicting safe starting doses.
  • A definitive algorithm for dose selection is currently not feasible.

    • Conclusions:

    • While preclinical data is vital, precise dose determination for FTIH studies remains challenging.
    • Existing rules of thumb are valuable but insufficient for a comprehensive decision tree.
    • Ongoing research is needed to improve the predictability of human dose selection.