Influence of continuous venovenous haemodiafiltration on the pharmacokinetics of tacrolimus in liver transplant recipients with small‐for‐size grafts

Kishino, Satoshi; Takekuma, Yoh; Sugawara, Mitsuru; Shimamura, Tsuyoshi; Furukawa, Hiroyuki; Todo, Satoru; Miyazaki, Katsumi

doi:10.1034/j.1399-0012.2003.00048.x

Cited by 9 publications

(7 citation statements)

References 12 publications

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“…In recent years, LDLT in adult patients with SFS grafts has become increasingly accepted [9] . With SFS grafts, it is considered that reduced functional liver mass is a necessity for adequate liver regeneration.…”

Section: Discussionmentioning

confidence: 99%

“…One possible explanation for the high variability of the optimal tacrolimus dose and its pharmacokinetics is the difference in graft size. In recent years, LDLT in adult patients with SFS grafts has become increasingly accepted [9] . However, questions related to this technique have arisen: What are the tacrolimus dosage requirements in SFS grafts which require adequate liver regeneration?…”

Section: Introductionmentioning

confidence: 99%

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Tacrolimus dosage requirements in living donor liver transplant recipients with small-for-size grafts

Liu¹,

Li²,

Xiang³

et al. 2009

WJG

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AIM:To investigate the tacrolimus dosage requirements and blood concentrations in adult-to-adult right lobe living donor liver transplantation (AALDLT) recipients with small-for-size (SFS) grafts. METHODS:During January 2007 and October 2008, a total of 54 cases of AALDLT with an observation period of 6 mo were enrolled in this study. The 54 patients were divided into two groups according to graftrecipient body weight ratio (GRBW): SFS grafts group (Group S, GRBW < 0.8%, n = 8) and non-SFS grafts group (Group N, GRBW ≥ 0.8%, n = 46). Tacrolimus 12-hour blood levels and doses were recorded during weeks 1, 2, 3 and 4 and months 2, 3, 4, 5 and 6 in group S and group N. Meanwhile, acute rejection rates, liver and renal function test results, and the number of potentially interacting medications were determined at each interval in the two groups. A comparison of tacrolimus dosage requirements and blood levels were made weekly in the first month post-surgery, and monthly from months 2 to 6. RESULTS:There were no differences in the demographic characteristics, acute rejection rates, liver and renal function test results, or the number of potentially interacting medications administered between the two groups. The tacrolimus dosage requirements in group S were significantly lower than group N at 2 wk (2.8 ± 0.4 mg/d vs 3.6 ± 0.7 mg/d, P = 0.006), 3 wk (2.9 ± 0.7 mg/d vs 3.9 ± 0.8 mg/d, P = 0.008), 4 wk (2.9 ± 0.8 mg/d vs 3.9 ± 1.0 mg/d, P = 0.023) and 2 mo (2.8 ± 0.7 mg/d vs 3.8 ± 1.1 mg/d, P = 0.033). Tacrolimus 12-h trough concentrations were similar between the two groups at all times except for 2 wk post-transplantation, when the concentrations were significantly greater in group S recipients than in group N recipients (11.3 ± 4.8 ng/mL vs 7.0 ± 3.8 ng/mL, P = 0.026).CONCLUSION: SFS grafts recipients have significantly decreased tacrolimus dosage requirements compared with non-SFS grafts recipients in AALDLT during the first 2 mo post-surgery.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tacrolimus dosage requirements in living donor liver transplant recipients with small-for-size grafts

Liu¹,

Li²,

Xiang³

et al. 2009

WJG

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“…In recent years, living donor liver transplantation in adult patients with small‐for‐size grafts has become increasingly accepted (7). In adult‐to‐adult living donor liver transplantation, the graft volume is inevitably much smaller than the ideal liver mass (standard liver volume) for the recipient's metabolic demand.…”

Section: Discussionmentioning

confidence: 99%

“…One possible explanation for the high variability of the optimal tacrolimus dose and its pharmacokinetics is difference in graft size. In recent years, living donor liver transplantation in adult patients with small‐for‐size grafts has become increasingly accepted (7). However, no optimal tacrolimus dosage regimen suitable for clinical use in transplant recipients with small‐for‐size grafts has yet been established.…”

mentioning

confidence: 99%

A nomogram for predicting the optimal oral dosage of tacrolimus in liver transplant recipients with small‐for‐size grafts

Kishino

Ohno

Shimamura

et al. 2006

Clinical Transplantation

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No optimal tacrolimus dosage regimen suitable for clinical use in liver transplant recipients has yet been established. The purpose of this study was to determine the factors affecting the optimal dosage and pharmacokinetics of tacrolimus in living donor liver transplantation, and a nomogram for optimal tacrolimus dosage in the immediate postoperative period for recipients with small-for-size grafts was constructed. Twenty-four liver transplant patients (nine males and 15 females) and 24 donors (10 males and 14 females) were enrolled in this study. Two studies were performed. In study 1, the effect of the actual ratio of graft volume to standard liver volume (GV/SV ratio) on the elimination half-life (T1/2) of tacrolimus in the immediate postoperative period was analysed, and a nomogram for estimating the optimal oral dose of tacrolimus required to reach a target concentration was established. In study 2, the effect of donor age on the recovery of hepatic function with ability of the graft to eliminate tacrolimus was analysed. In the immediate postoperative period, T1/2 of tacrolimus showed great variability between patients, with values ranging from 16.3 to 110.9 h. Graft size (GV/SV ratio) is important and could influence intraindividual variations in the optimal dosage and T1/2 of tacrolimus. The recovered T1/2 ratio (T1/2 ratio=T1/2 1-10 d/T1/2 30-40 d), this ratio being related to the recovery of hepatic function with ability of the graft to eliminate tacrolimus, showed great variability between patients, with values ranging from 1.08 to 4.21 (mean+/-SD, 1.95+/-0.81). Age of the donor is a major factor affecting the recovered ratio of the graft to metabolize tacrolimus. The nomogram that we have constructed, based on graft size (GV/SV ratio), will easily provide optimal dose for each patient with small-for-size graft in the early postoperative period.

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“…In general, the impact of dialysis on the concentration profile of therapeutic compounds is related to the extent of plasma protein binding. For highly protein-bound compounds, such as the immunosuppressive agent tacrolimus, which exists in its protein-bound form in blood at a rate of more than 98%, their concentration profiles are less affected by dialysis treatment than only slightly protein-bound compounds, such as gentamicin, which exists in its protein-bound form in plasma at a rate of less than 10% [2]. This difference in the impact of dialysis is largely caused by the fact that the peritoneum shows a permeation preference for molecules with a radius of less than 1.3nm [3], which is much smaller than the size of plasma proteins such as albumin and a 1 -acid glycoprotein.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of peritoneal dialysis of tolbutamide in rats under conditions of the plasma unbound fraction being increased

Makita

Aiba

Izuwa

et al. 2009

Biopharm & Drug Disp

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Peritoneal dialysis of a highly protein-bound compound, tolbutamide, was examined in rats to clarify whether the efficacy of the peritoneal dialysis of such compounds increases proportionally as their unbound fractions increase. As expected, it was shown that the tolbutamide concentration of the peritoneal dialysate rose as the unbound fraction of tolbutamide increased. However, the efficacy of peritoneal dialysis of tolbutamide was proportionally elevated only when the unbound fraction was slightly increased by sulfamethoxazole treatment. When the unbound fraction of tolbutamide was increased 7.8 times by sulfadimethoxine treatment, the dialysis efficacy was increased to only 58% of that expected. This discrepancy between the observed and expected values regarding dialysis efficacy was more marked when experiments were performed in rats with experimentally induced acute renal failure. Pharmacokinetic analysis indicated that the intrinsic dialysis clearance of tolbutamide decreased when its unbound fraction was greatly increased. These findings suggest that peritoneal dialysis may be mediated not only by passive diffusion, but also by concentration-dependent processes. The efficacy of the peritoneal dialysis of therapeutic compounds may be overestimated if the estimation is based only on their unbound fraction measured under control conditions.

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Influence of continuous venovenous haemodiafiltration on the pharmacokinetics of tacrolimus in liver transplant recipients with small‐for‐size grafts

Cited by 9 publications

References 12 publications

Tacrolimus dosage requirements in living donor liver transplant recipients with small-for-size grafts

Tacrolimus dosage requirements in living donor liver transplant recipients with small-for-size grafts

A nomogram for predicting the optimal oral dosage of tacrolimus in liver transplant recipients with small‐for‐size grafts

Efficacy of peritoneal dialysis of tolbutamide in rats under conditions of the plasma unbound fraction being increased

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