What question did this study set out to answer?

Investigate the pharmacokinetic basis of severe warfarin resistance in a patient requiring exceptionally high maintenance doses to achieve therapeutic anticoagulation.

March 1, 1993British Journal of Clinical PharmacologyOpen Access

High clearance of (S)‐warfarin in a warfarin‐resistant subject.

View Full Paper

Ask AI

Bookmark

Authors

HHHO HallakUniversity of Kentucky PWP J WedlundUniversity of Kentucky MMMW ModiUniversity of Kentucky

Discussion

Member takes

Implication

Case-control study demonstrates accelerated clearance of active (S)-warfarin in a warfarin-resistant individual, suggesting pharmacokinetic mechanisms drive extreme dosage requirements.

Key Points

Investigate the pharmacokinetic basis of severe warfarin resistance in a patient requiring exceptionally high maintenance doses to achieve therapeutic anticoagulation.
Evaluated a 30-year-old male propositus requiring 60 mg daily warfarin, two biological sisters, and 13 Black male controls.
Administered 5 mg intravenous vitamin K before and after two weeks of oral warfarin therapy (5 mg daily).
Measured oral clearance of (S)- and (R)-warfarin enantiomers and assessed systemic disposition of vitamin K and vitamin K epoxide across all subjects.
Mean systemic clearance of vitamin K was 114 ± 35 ml min⁻¹ before and 112 ± 40 ml min⁻¹ after warfarin across all subjects, while vitamin K epoxide AUC rose from 6.5 ± 5.4 to 139 ± 78 µg ml⁻¹ min.
The propositus showed markedly elevated (S)-warfarin oral clearance (14.5 ml min⁻¹) and an (S)/(R) clearance ratio of 2.6, exceeding control means (4.3 ± 1.1 ml min⁻¹ and 1.2 ± 0.2) by over 7 standard deviations.
One sister demonstrated similar pharmacokinetic changes, exhibiting an (S)-warfarin clearance of 16.2 ml min⁻¹ and an (S)/(R) clearance ratio of 2.7.

Cite This Study

Hallak et al. (1993) studied this question.

synapsesocial.com/papers/6a71560735aa2c282ce2a534 https://doi.org/10.1111/j.1365-2125.1993.tb05703.x

View Full Paper

Ask AI

Bookmark

Implication

Case-control study demonstrates accelerated clearance of active (S)-warfarin in a warfarin-resistant individual, suggesting pharmacokinetic mechanisms drive extreme dosage requirements.

High clearance of (S)‐warfarin in a warfarin‐resistant subject.

Discussion

Member takes

Implication

Key Points

Cite This Study

High clearance of (S)‐warfarin in a warfarin‐resistant subject.

Discussion

Member takes

Implication

Key Points

Cite This Study

Also Consider

Also Consider