Implications for body weight extremes in solid organ transplantation

Campara, Maya; Lourenço, Luís; Melaragno, Jennifer I.; Kaiser, Tiffany E.

doi:10.1002/phar.2493

Cited by 4 publications

(3 citation statements)

References 131 publications

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“…However, studies have shown that the tacrolimus concentration in adipose tissue is lower than expected for its degree of liphophillicity. 12 There exist several possible explanations for this observation. One theory is that tacrolimus is extensively distributed into erythrocytes and with increasing bodyweight, the blood plasma volume also increases, but to a lesser extent.…”

Section: Discussionmentioning

confidence: 99%

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Comparing weight‐based dosing of tacrolimus XR in obese and non‐obese renal transplant recipients

Breslin

Hedvat

Salerno

et al. 2021

Clinical Transplantation

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The recommended initial weight-based dose of extended-release (XR) tacrolimus (Envarsus XR) in kidney transplant recipients (KTR) is 0.14 mg/kg/day. However, no data exist regarding dosing recommendations for obese patients specifically. The aim of this study was to evaluate weight-based dosing requirements in a cohort of obese KTR who were initiated on de novo tacrolimus XR post-transplantation. The primary outcome was weight-based dosing requirements (mg/kg/day) on post-operative day (POD) 7 and 14. Of the 254 KTR, 81 (31%) were obese. The median therapeutic dose on POD7 was 0.1 versus 0.12 vs. 0.14 mg/kg/day in the BMI > 30 kg/m 2 , BMI 25-30 kg/m 2 , and BMI < 25 kg/m 2 , respectively, (p = .0001). This result was similar on POD14; median therapeutic dose was 0.09 versus 0.11 versus 0.15 mg/kg/day in the BMI > 30 kg/m 2 , BMI 25-30 kg/m 2 , and BMI < 25 kg/m 2 , respectively, (p < .001).Therapeutic dose on POD7 and POD14 based on ideal body was similar in all cohorts (p = .238, p = .923, respectively). This finding was supported by a strong linear relationship between ideal body weight (IBW) and therapeutic dose (r = .929). In both obese and non-obese KTR, IBW had a stronger correlation with the therapeutic dose for tacrolimus XR.

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Section: Discussionmentioning

confidence: 99%

“…Studies have identified elevated levels of alpha-1-acid glycoprotein, which binds tacrolimus affecting free drug concentrations. 12 Volume of distribution is also impacted, as adipose tissue increases with higher BMIs.…”

Section: Discussionmentioning

confidence: 99%

Comparing weight‐based dosing of tacrolimus XR in obese and non‐obese renal transplant recipients

Breslin

Hedvat

Salerno

et al. 2021

Clinical Transplantation

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“…Patients with obesity often exhibit a body composition with higher adipose content, potentially leading to increased distribution of lipophilic drugs, such as tacrolimus. [27][28][29] In fact, overexposure from initial doses of tacrolimus has been observed in several studies of patients with obesity, [30][31][32][33][34] suggesting that dosing of tacrolimus in transplant recipients is not one size fits all and that body weight may play a significant role in initial doses and correlation to tacrolimus levels.…”

Section: Discussionmentioning

confidence: 99%

Retrospective evaluation of LCP‐tacrolimus (Envarsus XR) dosing in de novo kidney transplant

Alzahrani,

Belcher,

Benken

et al. 2023

Clinical Transplantation

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IntroductionTacrolimus is known to exhibit significant inter‐ and intra‐patient pharmacokinetic (PK) and pharmacodynamic (PD) variability regarding therapeutic response. LCP‐tacrolimus (LCPT—Envarsus XR) was approved in 2018 for use as a de novo immunosuppressive agent in kidney transplants, but there is limited evidence to guide de novo dosing of LCPT in patients with obesity. The primary objective of this study was to evaluate the impact of different calculated weight‐based de novo LCPT dosing on early transplant outcomes.MethodsThis was a retrospective study of patients with obesity (BMI ≥ 30 kg/m2) who received a kidney transplant at the University of Illinois Hospital and Health System (UIH), between March 2019 and March 2021. Subjects were included if were age 18 years or older and received de novo LCPT throughout index hospitalization. The primary endpoint of this study was to compare correlations between the first tacrolimus trough level and dosing weight strategy (e.g., TBW, AdjBW, IBW).ResultsThere was a statistically significant, though modest, correlation between all three dosing strategies and the first tacrolimus trough level (TBW correlation coefficient = .431, p < .001; AdjBW correlation coefficient = .455, p < .001; IBW correlation coefficient = .465; p < .001). In regression modeling for supratherapeutic levels each additional .01 mg/kg increase in dose by TBW, AdjBW, and IBW increased the odds of a supratherapeutic level by 1.46, 1.34, and 1.24, respectively (p < .001).ConclusionsThe use of LCPT in kidney transplant recipients with obesity dosed using TBW demonstrated the strongest correlation with initial supratherapeutic tacrolimus levels. Larger prospective studies are needed to investigate the further impact of body weight on dosing regimens in the obese population.

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Solid organ transplant pharmacotherapy: Complicated and continually changing

Anger

Doligalski

2021

Pharmacotherapy

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Implications for body weight extremes in solid organ transplantation

Cited by 4 publications

References 131 publications

Comparing weight‐based dosing of tacrolimus XR in obese and non‐obese renal transplant recipients

Comparing weight‐based dosing of tacrolimus XR in obese and non‐obese renal transplant recipients

Retrospective evaluation of LCP‐tacrolimus (Envarsus XR) dosing in de novo kidney transplant

Solid organ transplant pharmacotherapy: Complicated and continually changing

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