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With the rapid development of nanotechnology, the research and development of nanomedicine has become one of the current development directions of drug innovation. The pharmacokinetic characteristics of nanomedicine are significantly different from general drugs because of the scale effect based on nanostructures, and pharmacokinetics studies of nanomedicine may be different from the general drugs. This article focuses on the research strategies and considerations on non-clinical pharmacokinetics of nanomedicine, including test agents, in vivo/in vitro assays, biological sample analysis, data evaluation and analysis etc., providing references for developers.
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Drug-drug interactions (DDI) change dose-response relationships, and may result in low efficacy or high toxicity, which are important considerations especially in medical practice with multiple-drug therapies. Predicting clinically significant drug interactions during new drug development is an important part of benefit and risk assessment in drug development and review. This article summarizes the purpose and significance of drug interactions in new drug development, the main content and precautions of DDI studies in vivo and in vitro. Drug interaction studies on novel drug approvals for 2020 in the National Medical Products Administration (NMPA) and US Food and Drug Administration (USFDA) are examined, respectively. It aims to provide reference for DDI studies and regulatory reviews in new drug development in our country.
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OBJECTIVE@#To review the clinical features of a male twin affected with glutaric academia type I (GA-I) and analyze the variations of glutaryl-CoA dehydrogenase (GCDH) gene.@*METHODS@#Clinical data of the pair of twins and their parents were collected. Genomic DNA was extracted from peripheral blood samples, and variants of GCDH genes were detected by capture sequencing using a customized panel. Variants of the twins and their parents were verified by Sanger sequencing.@*RESULTS@#The level of glutaric acyl carnitine (C5DC + C6OH) was 3.26 μmol/L in the male twin. The relative level of glutaric acid in urine was 547.51 by gas chromatography mass spectrometry analysis. Cerebral ultrasonography showed that the patient had subependymal hemorrhage, but no serious clinical manifestation was noted. After treating with special formula milk powder and L-carnitine, the boy showed good growth and development. Two heterozygous variants of the GCDH gene were detected in the patient, among which c.416C>G was suspected to be pathogenic, while c.109_110delCA was unreported. The variants were respectively inherited from his parents. The twin girl only carried the c.416C>G variant.@*CONCLUSION@#GA-I can be diagnosed by mass spectrometry, urine gas chromatographic mass spectrometry, imaging as well as genetic diagnosis. Early diagnosis and intervention is important.