Abstract：
PURPOSE:The pharmacokinetics of orally administered immediate-release, twice-daily (BID) and modified-release, once-daily (QD) formulations of tacrolimus have high interindividual variability. We investigated factors affecting interindividual variability of tacrolimus bioavailability in renal transplant patients. METHODS:Ninety-seven Japanese renal transplant patients (47 patients on tacrolimus BID and 50 patients on tacrolimus QD) were enrolled in this study. The tacrolimus absolute bioavailability was calculated using the area under the concentration-time curve from 0 to 24 h (AUC0-24) after continuous intravenous infusion and oral formulations of tacrolimus in the same recipient. RESULTS:The median (quartile 1-quartile 3) tacrolimus relative bioavailability for recipients with the CYP3A5*1 or CYP3A5*3/*3 alleles was significantly lower for the tacrolimus QD group [9.1 % (6.3-10.7 %) and 15.4 % (11.5-18.7 %), respectively] than for the tacrolimus BID group [12.6 % (9.9-14.2 %) and 19.3 % (16.5-24.8 %), respectively] (P = 0.004 and 0.028, respectively). Consequently, tacrolimus absolute bioavailability was lowest for recipients with the CYP3A5*1 allele taking tacrolimus QD. The CYP3A5 polymorphism had no impact on the dose-adjusted AUC0-24 of tacrolimus in patients on continuous intravenous infusion (P = 0.906). CONCLUSION:The larger interindividual variability of tacrolimus bioavailability for oral formulations appears to be due to the effects of the CYP3A5 polymorphism and the tacrolimus oral formulation. These factors should therefore be taken into account when determining individualized tacrolimus dosing.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Niioka T,Kagaya H,Miura M,Numakura K,Saito M,Inoue T,Habuchi T,Satoh Sdoi
10.1007/s00228-013-1514-8subject
Has Abstractpub_date
2013-09-01 00:00:00pages
1659-65issue
9eissn
0031-6970issn
1432-1041journal_volume
69pub_type
临床试验,杂志文章abstract：OBJECTIVE:To compare the efficacy of activated charcoal and gastric lavage in preventing the absorption of moclobemide, temazepam, and verapamil 30 min after drug ingestion. METHODS:In this randomized cross-over study with three phases, nine healthy volunteers received a single oral dose of 150 mg moclobemide, 10 mg t...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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journal_title：European journal of clinical pharmacology
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abstract：:As a target group, geriataric patients were selected for pharmacokinetic studies with terodiline (Mictrol), an anticholinergic and calcium antagonist drug effective in the treatment of urinary incontinence. The single-dose kinetics in the geriatric patients (mean age 82 years) differed significantly from that previous...
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journal_title：European journal of clinical pharmacology
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journal_title：European journal of clinical pharmacology
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journal_title：European journal of clinical pharmacology
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