European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Jan 2017
Randomized Controlled TrialEffect of bosutinib on the absorption of dabigatran etexilate mesylate, a P-glycoprotein substrate, in healthy subjects.
Bosutinib, a dual Src and Abl tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia, demonstrated concentration-dependent inhibitory effects on P-glycoprotein (P-gp)-mediated digoxin efflux in vitro, suggesting that bosutinib may inhibit P-gp substrates. The effect of bosutinib on dabigatran etexilate mesylate (EM) absorption, a P-gp substrate, was evaluated. ⋯ These data demonstrate that single doses of bosutinib do not affect dabigatran exposure, suggesting that bosutinib is not a clinical inhibitor of P-gp.
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Eur. J. Clin. Pharmacol. · Jan 2017
Adverse drug events in patients with advanced chronic conditions who have a prognosis of limited life expectancy at hospital admission.
Adverse drug events (ADEs) lead to adverse clinical outcomes such as hospitalization. There is little information about the characteristics of ADEs in patients with advanced chronic conditions and have a prognosis of limited life expectancy. This study aimed to evaluate (i) the prevalence of ADEs at the time of admission to hospital, (ii) the causality, severity, and preventability of the ADEs, and (iii) the clinical and pharmacological characteristics associated with the ADEs. ⋯ ADEs are common, largely preventable, and implicated in the hospitalization of patients who require palliative care.
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Eur. J. Clin. Pharmacol. · Jan 2017
Randomized Controlled TrialEffect of aprepitant, a moderate CYP3A4 inhibitor, on bosutinib exposure in healthy subjects.
Bosutinib is an oral, dual Src and Abl tyrosine kinase inhibitor (TKI) approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia resistant or intolerant to prior TKI therapy. Bosutinib is primarily metabolized by cytochrome P450 (CYP) 3A4, suggesting drug interaction potential with other CYP3A4 modulators. This open-label, randomized, 2-sequence, 2-period crossover study assessed the effect of single-dose aprepitant, a moderate CYP3A4 inhibitor, on the single-dose pharmacokinetic profile of oral bosutinib 500 mg. ⋯ In healthy volunteers, administering a single dose of aprepitant increased the AUC and C max following a single dose of bosutinib by 99 and 53 %, respectively. These results are consistent with a moderate CYP3A4 inhibitor effect of aprepitant on bosutinib (Trial Registration: ClinicalTrials.gov NCT02058277).