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Understanding how a drug's concentration fluctuates within the body over time is crucial in pharmacokinetics, particularly with multiple oral doses. A graphical representation of multiple oral dosages provides insight into these dynamics. Typical accumulation curves of a drug's concentration in the body reveal a sawtooth pattern, indicating periodic peaks and troughs correlating with each dose administration and the drug's subsequent elimination.The plasma concentration at any time during an...
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Predicting prolonged dose titration in patients starting warfarin.

Brian S Finkelman1,2, Benjamin French1, Luanne Bershaw1

  • 1Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Pharmacoepidemiology and Drug Safety
|July 27, 2016
PubMed
Summary

Predicting prolonged warfarin dose titration is challenging. Traditional clinical, social, and genetic factors do not accurately forecast this period, necessitating new approaches for patient management.

Keywords:
decision analysispharmacoepidemiologypharmacogeneticsrisk assessmenttreatment effectivenessvalidity (epidemiology)warfarin

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Area of Science:

  • Pharmacology and Clinical Pharmacy
  • Health Services Research

Background:

  • Warfarin therapy requires a dose-titration period, increasing risks of thromboembolic and bleeding events.
  • Accurate prediction of prolonged titration could guide the use of alternative anticoagulants.

Purpose of the Study:

  • To develop and validate a predictive model for prolonged warfarin dose titration.

Main Methods:

  • A Cox regression model was developed in a prospective cohort and validated externally.
  • Predictors included clinical, social factors; genetic factors were also assessed.
  • Prolonged titration was defined as >12 weeks.

Main Results:

  • The final model included indication, insurance, doctor visits, smoking, and heart failure.
  • Model performance (AUC) was 0.66 in derivation and 0.59 in validation cohorts.
  • Genetic factors did not improve predictive accuracy; model utility was limited.

Conclusions:

  • Prolonged warfarin dose titration cannot be accurately predicted using current clinical, social, or genetic predictors.
  • Future prediction models must account for clinical site and temporal heterogeneities.