Population Pharmacokinetic Investigation for Optimization of Amiodarone Therapy in Japanese Patients

Araki, Ryosuke; Yukawa, Eiji; Nakashima, Mihoko N.; Fukuchi, Hiromitsu; Sasaki, Hirokazu; Yano, Katsusuke; Nakashima, Makoto

doi:10.1097/ftd.0b013e318239a728

Cited by 12 publications

(11 citation statements)

References 26 publications

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“…In the current study, male patients had an increased risk of cancer, but female patients did not. One possible explanation for this difference is that there is a 37% higher clearance rate of amiodarone in females than in males because of differences in cytochrome P450 3A4 activity and the percentage of body fat 25. In addition, hormonal stimuli might play a role in the gender difference.…”

Section: Discussionmentioning

confidence: 99%

“…One possible explanation for this difference is that there is a 37% higher clearance rate of amiodarone in females than in males because of differences in cytochrome P450 3A4 activity and the percentage of body fat. 25 In addition, hormonal stimuli might play a role in the gender difference. The increased cancer incidence within 1 year of treatment with amiodarone may be due to a surveillance bias.…”

Section: Discussionmentioning

confidence: 99%

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Amiodarone and the risk of cancer

Chou

et al. 2013

Cancer

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BACKGROUND:In postmarketing surveillance, the US Food and Drug Administration has reported the development of lung masses, thyroid cancer, and skin cancer after amiodarone therapy. METHODS: Using the Taiwan National Health Insurance Research database, the authors conducted a population-based cohort study. Patients who were treated with amiodarone between 1997 and 2008 were enrolled. Those with antecedent cancer were excluded. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort with that of the general population. A multivariate Cox regression model was used to evaluate the association between cumulative defined daily doses (cDDDs) of amiodarone and cancer occurrence. RESULTS: The study included 6418 subjects, with a median follow-up of 2.57 years. A total of 280 patients developed cancer. The risk of cancer increased with borderline significance (SIR, 1.12; 95% confidence interval [95% CI], 0.99-1.26 [P ¼ .067]). Male patients had a higher risk (SIR, 1.18; 95% CI, 1.02-1.36 [P ¼ .022]). The total cohort of patients and the male patients with > 180 cDDDs within the first year were found to have SIRs of 1.28 (95% CI, 1.00-1.61; P ¼ .046) and 1.46 (95% CI, 1.11-1.89; P ¼ .008), respectively. After adjustment for age, sex, and comorbidities, the hazards ratio was 1.98 (95% CI, 1.22-3.22; P ¼ .006) for the high tertile of cDDDs compared with the low tertile. CONCLUSIONS: The results of the current study indicate that amiodarone may be associated with an increased risk of incident cancer, especially in males, with a dose-dependent effect.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Amiodarone and the risk of cancer

Chou

et al. 2013

Cancer

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“…22 Amiodarone is metabolized by cytochrome P450 (CYP) 3A4 and CYP2C8 in the liver, and amiodarone and its metabolite are both highly lipophilic and may accumulate in many tissues, especially adipose tissue. 23 A pharmacokinetic investigation in Japan revealed 37% faster amiodarone clearance in females compared with males. The proposed mechanism related to the impacts of estrogen and progesterone on CYP3A4, higher CYP3A4 activity in hepatic microsomes of females, and lower body fat in females.…”

Section: Discussionmentioning

confidence: 98%

Amiodarone-Associated Optic Neuropathy

et al. 2015

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“…Females have increased levels of cytochrome P450 3A4, the most abundant phase I drug-metabolizing enzyme in humans, as well as an increased percentage of body fat (10% -13% versus 2% -5% in males). These may work in combination to increase the clearance rate of amiodarone ~37% [43]. Differences in hormonal stimuli may also play a role.…”

Section: All Cancers 280mentioning

confidence: 99%

Amiodarone Therapy for Cardiac Arrhythmias: Is It Associated with the Development of Cancers?

Mali¹,

Salzman²,

Vidaillet³

et al. 2014

WJCD

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Amiodarone is used worldwide to treat cardiac arrhythmias, as well as highly symptomatic cases of atrial fibrillation. With this expanded use, especially following its 1985 United States Food and Drug Administration approval, and its use as a long-term therapy in common practice, reports of cancers temporarily related to amiodarone have begun to increase. Animal studies, several clinical trials, numerous case reports, and a population-based cohort study have suggested that cancers may be associated with amiodarone use. This review focuses on the ever increasing evidence in the literature that suggests amiodarone therapy, especially with long-term use, may increase the potential risk of cancer development. It also expresses the need for more definitive studies to be conducted to provide clinicians with a clear answer to this important question.

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Population Pharmacokinetic Investigation for Optimization of Amiodarone Therapy in Japanese Patients

Abstract: The authors developed new population pharmacokinetic parameters. Clinical application of the findings in the present study to patient care may permit selection of an appropriate initial maintenance dose, thus enabling the clinician to achieve a desired therapeutic effect.

Cited by 12 publications

References 26 publications

Amiodarone and the risk of cancer

Amiodarone and the risk of cancer

Amiodarone-Associated Optic Neuropathy

Amiodarone Therapy for Cardiac Arrhythmias: Is It Associated with the Development of Cancers?

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