Effect of Serum Triglyceride Concentration on the Fluctuation of Whole Blood Concentration of Cyclosporin A in Patients.
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- NAKAMURA Tsutomu
- Department of Hospital Pharmacy, School of Medicine, Kobe University
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- KAKUMOTO Mikio
- Department of Hospital Pharmacy, School of Medicine, Kobe University
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- SAKAEDA Toshiyuki
- Department of Hospital Pharmacy, School of Medicine, Kobe University
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- NAGAHIRO Kazumi
- Department of Hospital Pharmacy, School of Medicine, Kobe University
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- OHMICHI Rumi
- Department of Hospital Pharmacy, School of Medicine, Kobe University
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- YAMASHITA Kazuhiko
- Department of Hospital Pharmacy, School of Medicine, Kobe University
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- NISHIGUCHI Kohshi
- Department of Hospital Pharmacy, School of Medicine, Kobe University
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- HIRAI Midori
- Department of Clinical Pharmacy, Kobe Pharmaceutical University
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- OKUMURA Katsuhiko
- Department of Hospital Pharmacy, School of Medicine, Kobe University
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Abstract
The methodology to distinguish the patients showing considerable fluctuation of the whole blood concentration of cyclosporin A (CYA) was investigated from a viewpoint of laboratory test values. First, we retrospectively examined the CYA trough blood concentrations monitored continuously. The patients were classified into three groups by the fluctuation of CYA trough blood concentrations during the examination period (Cmax/Cmin): Group 1(Cmax/Cmin=100—200%; n=21), Group 2 (Cmax/Cmin=200—300%; n=25), and Group 3 (Cmax/Cmin=more than 300%; n=32). In the laboratory tests examined, the serum triglyceride concentrations were considerably different among the groups, and it was the highest in Group 3. Next, to elucidate the effect of serum triglyceride concentration on the CYA blood concentration, in vivo pharmacokinetic studies after single intravenous or repetitive oral administration of CYA were conducted in the model rats with pseudo-hypertriglyceridemia, hypocythemia, and acute renal failure. Only in pseudo-hypertriglyceridemia rats, the CYA blood concentration after a single intravenous injection was significantly higher than that in normal rats because of the restriction of CYA distribution to the extravascular tissues. On the other hand, the increase in the serum triglyceride concentration did not affect the fluctuation of CYA trough blood concentration after repetitive oral administration. Taken together, the fluctuation of CYA trough blood concentrations observed in the clinical situation could be due to the fluctuation of serum triglyceride concentration, and the patients with such fluctuation of serum triglyceride concentrations might also be distinguishable by the higher concentration of serum triglyceride in laboratory tests.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 24 (6), 683-687, 2001
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001204628542720
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- NII Article ID
- 110003638538
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- NII Book ID
- AA10885497
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- COI
- 1:CAS:528:DC%2BD3MXktFygt7w%3D
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 5793420
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- PubMed
- 11411559
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed