2023-10-16 バッファロー大学(UB)
◆米国バッファロー大学の研究者らによる臨床研究は、高齢の腎移植患者は、免疫抑制薬を若い患者と同じように分解しないことを示唆しています。これにより、これらの薬物が高齢者の体内に長く留まり、有害な副作用、例えば振戦が増加する可能性があります。この知見に基づき、高齢者の腎移植患者への免疫抑制薬の投与方法に調整が必要かもしれず、副作用を最小限に抑えることができるかもしれません。高齢者への腎移植の増加に伴い、この研究は今後ますます重要となるでしょう。
<関連情報>
- https://www.buffalo.edu/news/releases/2023/10/Olderkidneytransplantpatients.html
- https://ascpt.onlinelibrary.wiley.com/doi/full/10.1111/cts.13495?campaign=wolearlyview
安定した黒人と白人の腎移植レシピエントにおけるタクロリムスとミコフェノール酸の薬物動態と年齢との関連: 健康格差への示唆 Age associations with tacrolimus and mycophenolic acid pharmacokinetics in stable Black and White kidney transplant recipients: Implications for health inequities
Kathleen M. Tornatore, Kristopher Attwood, Rocco C. Venuto, Brian Murray
Clinical and Translational Science Published: 24 February 2023
http:https://doi.org/10.1111/cts.13495
Abstract
Tacrolimus (TAC) and mycophenolic acid (MPA) provide maintenance immunosuppression and is dosed empirically in elderly kidney transplant recipients (KTRs) resulting in health inequities. Limited immunosuppressive pharmacokinetics are available comparing adult ages. This secondary analysis compared TAC and MPA pharmacokinetics and adverse effects (AEs) among young, middle-aged, and elderly Black and White KTRs. The 12-h TAC and MPA pharmacokinetics with AE evaluation were conducted in 67 stable KTRs greater than or equal to 6 months post-transplant. TAC regimens were adjusted to target troughs. MPA regimens were adjusted using clinical response. Participants were: young: less than or equal to 40 years; middle age: greater than 40 to 60 years, and elderly greater than 60 years. Noncompartmental pharmacokinetic analysis determined area under the concentration-time curve 0–12 h (AUC0-12h), clearance (CL), and CL/body mass index (BMI) with 0-h troughs. MPA enterohepatic recirculation (EHR), MPA-AUC6-12h/MPA-AUC0-12h, and MPA glucuronide (MPAG)-AUC0-12h/MPA-AUC0-12h were determined. Univariate analysis of variance (ANOVA) was conducted using SAS version 9.4. No group differences were noted for estimated glomerular filtration rate, MPA, and TAC doses. EHR was reduced in elderly with decreased MPA-AUC6-12h/MPA-AUC0-12h (p = 0.049) and increased MPAG-AUC0-12h/MPA-AUC0-12h (p = 0.036). MPA troughs (p = 0.045) were reduced in the elderly. TAC CL/BMI (p = 0.043) was reduced in the elderly. For therapeutic MPA AUC0-12h: 30–60 mg·h/L, 34.3% KTRs achieved this target with 55.2% greater than the therapeutic range. 77.6% KTR were in the TAC AUC0-12h target: 100–190 ng·h/mL and 19.4% were below this range with no age relationship. In 44% young, 26% middle-age and 7.8% elderly subjects achieved target AUC0-12h for both medications (p = 0.036). Neurologic AEs were manifested in the elderly (p = 0.014). Immunosuppressive pharmacokinetics demonstrated age-related differences with reduced TAC CL/BMI and MPA EHR and increased neurologic AE in the elderly. This immunosuppressive regimen may require age-adjusted individualization to optimize allograft function.
