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settings the Cmax plasma values of unchanged drug and alcohol
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plasma, BChE represents approximately 0.1% of total serum proteins
(Chatonnet and Lockridge, 1989). The estimated prevalence of the
wild-type homozygous BChE genotype in white populations is ap-
proximately 95%. To date, approximately 65 genetic variants of
human BChE have been identified, and the most predominant variants
are the K, A (atypical), and J variants. Individuals with this genotype
show reduced enzyme activity caused by a depletion of the circulating
BChE molecules. There are also approximately 20 silent genotypes
characterized by the near complete absence of BChE activity. In
addition, other rare variants (e.g., C5ϩ, Cynthiana and Johannesburg)
with increased BChE activity have been also identified (Table 3).
Although the influence of the BChE genotype on aclidinium disposi-
tion has not been studied, one could speculate that in those patients
with genetic BChE variants with decreased activity, the rate of acli-
dinium ester hydrolysis would be reduced. However, it is not expected
to be clinically significant as a result of the important nonenzymatic
hydrolysis (t1/2, 1.2 h) at physiological pH. The results obtained in this
study show that human BChE is the most important enzyme involved
in the enzymatic hydrolysis of aclidinium and that this process takes
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minimal systemic exposure after inhaled administration: identification of (3R)-3-{[hydroxy
(di-2-thienyl)acetyl]oxy}-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (aclid-
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Acknowledgments. We thank Francisco Jime´nez for technical
support.
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Address correspondence to: Joan Albertí, Department of Pharmacokinetics
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Llobregat, Barcelona, Spain. E-mail: joan.alberti@almirall.com
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