Evaluation of tacrolimus-related CYP3A5 genotyping in China: Results from the First External Quality Assessment Exercise.

BACKGROUND: Tacrolimus is the most widely used immunosuppressant in solid organ transplant patients. The cytochrome P450 3A5 (CYP3A5) has been proved to be associated with tacrolimus dose requirement. Molecular detection for CYP3A5 genotyping is demanded for the optimization of treatments of tacrolimus. METHODS: To achieve the consistency and accuracy of the testing results, the Chinese National Center for Clinical Laboratories (NCCL) organized a national external quality assessment(EQA) program to evaluate the performance of laboratories providing CYP3A5 genotyping. Ten validated DNA samples covering the common genetic polymorphisms of CYP3A5 were delivered to 33 voluntary laboratories, and their detecting results and clinical written reports were evaluated. RESULTS: Thirty-three datasets were received. The corresponding analytical sensitivity was 95.9% (285/297 challenges; 95% confidence interval: 93.0%-97.9%), and the analytical specificity was 95.3% (346/363; 95% confidence interval: 92.6%-97.2%). Thirty of the participating laboratories correctly identified the CYP3A5 allele status for all EQA samples. Three laboratories made genotyping errors, and 2 of them failed to detect any of the homozygotes such as *1/*1 and *3/*3. Twenty-eight CYP3A5*3 tests reports were submitted, but many reports showed a shortage of essential information. No reports fulfilled all the consensus recommendations for pharmacogenetic test result reporting. CONCLUSION: The EQA program highlighted the necessity for an improvement in the accuracy of genotyping for some of the laboratories and a greater education on the reporting of CYP3A5 genotyping results.

Efficacy and Safety of Vinpocetine as Part of Treatment for Acute Cerebral Infarction: A Randomized, Open-Label, Controlled, Multicenter CAVIN (Chinese Assessment for Vinpocetine in Neurology) Trial.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of intravenous vinpocetine administration as part of a comprehensive treatment for acute cerebral infarction in a Chinese population. METHODS: 610 acute cerebral infarction patients were randomized into two groups: the vinpocetine group (469 patients) received cytidine disphosphate choline 0.4-0.5 g in combination with aspirin 75-100 mg or clopidogrel 75 mg once daily, plus vinpocetine 30 mg intravenously once daily for 7 days, while the control group (141 patients) received cytidine disphosphate choline 0.4-0.5 g in combination with aspirin 75-100 mg or clopidogrel 75 mg once daily for 7 days. Additionally, patients received medications for symptoms such as hypertension, hyperglycemia, hyperlipidemia, and intracranial hypertension when necessary. Mini-Mental State Examination (MMSE), National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale, and Barthel Index (BI) scores and transcranial doppler (TCD) were assessed at baseline, 7, 14, and 90 days after treatment. Adverse events (AEs) and abnormalities in blood, urine, liver, and kidney function were monitored. RESULTS: MMSE, NIHSS, and BI scores were significantly higher in the vinpocetine group than in the control group 90 days after treatment, indicating significantly improved cognitive skill, neurological function, and quality of life (QOL) in the vinpocetine group versus the control group. Importantly, such effects of vinpocetine were maintained over time. In addition, TCD monitoring showed significantly increased cerebral blood flow associated with vinpocetine versus control. No significant difference in safety was noted between the two groups. CONCLUSIONS: When used as part of treatment for acute cerebral infarction, vinpocetine improves patients' cerebral blood flow, cognitive quality, neurological functions, and QOL. Vinpocetine could be an effective and safe component of treatment regimen for acute cerebral infarction.