초록

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PIPETapps: A compilation of Pharmacometrics R Shiny apps using cloud computing tools: Using AWS, R Shiny, and NONMEM

Cloud computing allows pharmacometricians to access advanced hardware, network, and security resources available to expedite analysis and reporting.

• R shiny App이 많다.
• 대부분이 설치를 필요로 하지 않기 때문에, 학생과 연구원을 위한 약리학 교육에도 좋다.
• NONMEM, PsN, Grid Engine을 고성능의 패러럴 컴퓨팅도 가능하다.

Cloud-based computing environments are available at a fraction of the time and effort when compared to traditional local datacenter-based solutions. This tutorial explains how to get started with building your own personal cloud computer cluster using Amazon Web Services (AWS), NONMEM, PsN, Grid Engine, and Sonic.

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592533/

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DURATION OF ORAL BIOABAILABILITY ENHANCEMENT OF LOPERAMIDE BY HM30181AK,

A NOVEL P-GLYCOPROTEIN INHIBITOR, IN HEALHTY KOREAN MALE SUBJECTS

Namyi Gu, MD1, Tae-Eun Kim, MD1, Yu-Jung Cha, MD1, Kyung-Mi Park, PhD2, Seo Hyun Yoon, PhD1, Joo-Youn Cho, PhD1, Sang-Goo Shin, MD, PhD1, In-Jin Jang, MD, PhD1, Kyung-Sang Yu, MD, PhD1

1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine, 2Hanmi Pharm. Co., Ltd., Seoul

BACKGROUND: HM30181AK is a novel P-glycoprotein (P-gp) inhibitor under clinical development for enhancement of oral bioavailability of p-gp substrates. The objective of this study was to investigate the duration and proper dose of HM30181AK tableton P-gp using loperamide as a probe drug.

METHOD: This was a randomized, 5-period, open-label, parallel design study. Thirty-one subjects were randomized to 1, 5, 10, 15, 60 mg HM30181AK dose groups and orally administered 16 mg loperamide as a single oral dose on Day 1, 4, 8, 11, 15. HM30181AK was administered with loperamide simultaneously on Day 4. Serial blood samples were collected over 72 hours after each loperamide administration to assess the bioavailability of loperamide. Plasma concentrations of loperamide were determined by liquid chromatography-tandem mass spectrometry. Log transformed AUC(0-72h)s of loperamide in period II (Day 4-7), III (Day 8-11), IV (Day 11-14) and V (Day 15-18) were compared with period I (Day 1-4) using a mixed effect model with period effect fixed.

RESULTS: From period II, AUC(0-72h)s of loperamide were increased in all dose groups until period V, following 15 days after administration of HM30181AK, with the maximal geometric mean ratios (90% confidence interval) of 1.50(1.23-1.84), 1.43(1.17-1.74), 1.54(1.13-2.10), 1.77(1.40-2.24) and 1.47(1.13-1.92) in HM30181AK 1, 5, 10, 15, and 60 mg dose groups, respectively. AUC(0-72h) of loperamide in Period II, HM30181AK-coadministered period, increased with HM30181AK doses and reached maximum values after administration of 10 mg HM30181AK. The correlation between pharmacokinetics of HM30181AK and AUC(0-72h) of loperamide was not significant.

CONCLUSION: The inhibitory effect of HM30181AK on p-gp was sustained for 15 days after single administration of dose of 1-60 mg. The inhibition of p-gp was speculated to be saturated on dose of 10 mg.

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