2004 Fiscal Year Final Research Report Summary
Study of the pharmacogenetic analysis of an arachidonic acid cascade in asthma and the made-to-order treatment for an asthma patient
| Project/Area Number |
15591101
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Gifu University |
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Principal Investigator |
TERAMOTO Takahide Gifu University, hospital attached to the medical department, Assistant, 医学部附属病院, 助手 (60324307)
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| Co-Investigator(Kenkyū-buntansha) |
FUKAO Toshiyuki Gifu University, graduate school medicine postgraduate course, Associate professor, 大学院・医学研究科, 助教授 (70260578)
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| Project Period (FY) |
2003 – 2004
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| Keywords | bronchial asthma / Arachidonic acid cascade / Gene analysis / leukotriene C4 synthase / pranlukast / Urinary leukotriene E_4 / Urinary 11-dehydro-thromboxane B_2 |
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| Research Abstract |
We reported two points of the following :
1)Blood samples from bronchial asthma children were obtained at approximately 20 time points per adult (n=121) and 2 or 3 time points per child (n=54). Population pharmacokinetic analysis was performed with use of NONMEM. The concentration-time course of pranlukast was described by using a one-compartment model with first-order absorption. The robustness of the final model was evaluated by using 200 bootstrap samples.
In results Apparent Clearance (CL/F) was 1.81 and 1.14 L/h/kg in children and adults, respectively. According to subgrouping of the children, no significant difference was observed in CL/F between infants (3 to 6 years old) and schoolchildren (7 to 14 years old). The interindividual variability of CL/F accounted for 48.7%. The additive and proportional residual variability were 7.33 ng/mL and 73.8%, respectively. All the fixed effect parameters fell within 10% of the bootstrapped mean.
2)We measured Urinary LTE_4 and 11DTXB_2 levels
… More
by enzyme immunoassay (ETA) and radioimmunoassay (RIA), respectively. Urine samples from asthmatic children were measured during the stable condition and during an acute attack. In result, Urinary LTE_4 levels during an acute attack (median 476 pg/mg creatinine ; range 191-1100 pg/mg creatinine) and during the stable condition (median 332 pg/mg creatinine ; range 128-965 pg/mg creatinine) were significantly higher (P<0.05) than those of controls (median 233 pg/mg creatinine ; range 103-389 pg/mg creatinine). Urinary 11DTXB_2 levels during an acute attack and during the stable condition (median 1666 (range 110-5105) and 1009 (range 46-6070) pg/mg creatinine, respectively) were significantly higher (P<0.05) than those of controls (median 252 pg/mg creatinine ; range 41-716 pg/mg creatinine). Comparing different stages of asthma, LTE_4 levels during an acute attack were significantly higher (P<0.05) than during the stable condition ; however, there was no difference in urinary TXB_2 levels.
In Conclusions : The present findings suggest that high levels of CysLTs and TXA_2 are associated with the pathogenesis of bronchial asthma. The measurement of urinary LTE_4 and 11DTXB_2 would be useful in understanding the individual pathogenesis of asthmatic children. Less
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Research Products
(12 results)
