Key result
Apixaban requires ~30% dose reduction in the elderly to match healthy adult PK exposure.
Why the study?
Apixaban has a limited therapeutic index and its pharmacokinetics may be altered in elderly populations and those with renal or hepatic impairment, necessitating dosage adjustments.
Does physiologically based pharmacokinetic modeling predict the required apixaban dosage adjustments to achieve equivalent exposure in elderly populations and those with renal or hepatic impairment compared to healthy adults?
Does physiologically based pharmacokinetic modeling predict the required apixaban dosage adjustments to achieve equivalent exposure in elderly populations and those with renal or hepatic impairment compared to healthy adults?
Physiologically based pharmacokinetic modeling suggests that apixaban doses should be significantly reduced in Chinese elderly patients and those with renal or hepatic impairment to match the exposure levels of healthy adults.
Modeling suggests apixaban dose reductions in elderly with organ impairment; hypothesis-generating and requires clinical validation before practice change.
BACKGROUND: Apixaban is a factor Xa inhibitor with a limited therapeutic index that belongs to the family of oral direct anticoagulants. The pharmacokinetic (PK) behavior of apixaban may be altered in elderly populations and populations with renal or hepatic impairment, necessitating dosage adjustments. METHODS: This study was conducted to examine how the physiologically based pharmacokinetic (PBPK) model describes the PKs of apixaban in adult and elderly populations and to determine the PKs of apixaban in elderly populations with renal and hepatic impairment. After PBPK models were constructed using the reported physicochemical properties of apixaban and clinical data, they were validated using data from clinical studies involving various dose ranges. Comparing predicted and observed blood concentration data and PK parameters was utilized to evaluate the model's fit performance. RESULTS: Doses should be reduced to approximately 70% of the healthy adult population for the healthy elderly population to achieve the same PK exposure; approximately 88%, 71%, and 89% of that for the elderly populations with mild, moderate, and severe renal impairment, respectively; and approximately 96%, 81%, and 58% of that for the Child Pugh-A, Child Pugh-B, and Child Pugh-C hepatic impairment elderly populations, respectively to achieve the same PK exposure. CONCLUSION: The findings indicate that the renal and hepatic function might be considered for apixaban therapy in Chinese elderly patients and the PBPK model can be used to optimize dosage regimens for specific populations.
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Xu et al. (2023) studied Hepatic impairment, renal impairment, elderly. Apixaban vs. Healthy adults was evaluated on Pharmacokinetic exposure (AUC and Cmax). To achieve equivalent pharmacokinetic exposure, apixaban doses should be reduced to approximately 70% for healthy elderly, 71-89% for elderly with renal impairment, and 58-96% for elderly with hepatic impairment compared to healthy adults.
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