Pharmacokinetics in Stable Kidney Transplant Recipients After Conversion From Twice-Daily to Once-daily Tacrolimus Formulations

Hooff, Johannes van; Walt, Isak Van der; Kallmeyer, J.C.; Miller, Derek M.; Dawood, Shabbir; Moosa, Mohammed Rafique; Christiaans, M. H. L.; Karpf, Carmen; Undre, Nasrullah

doi:10.1097/ftd.0b013e318244a7fd

Cited by 46 publications

(44 citation statements)

References 12 publications

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“…Two studies reported significantly less within-subject variation in exposure after conversion to MR tacrolimus but provided no actual numerical data [43,60]. Another study reported similar within-and betweensubject variability between Prograf Ò and Advagraf Ò formulations [31]. No study to date has looked at withinpatient variability in exposure to Envarsus Ò XR.…”

Section: Xrmentioning

confidence: 94%

“…Three studies reported that within-subject variability [percentage coefficient of variation (% CV)] in AUC 0-24 or C min decreased significantly following conversion from Prograf Ò to Advagraf Ò [28,35,43], while two studies could find no significant difference [31,45]. Conversion from Prograf Ò to Advagraf Ò resulted in a significant reduction in within-subject variability in tacrolimus AUC 0-24 from 14.1 to 10.9 % (but no reduction in C min ) in a study involving 40 stable kidney transplant recipients, assessed using five AUC values for each dosing regimen [28], and a reduction in tacrolimus C min from 14.0 to 8.5 % in a study involving 129 stable kidney transplant recipients [35].…”

Section: Xrmentioning

confidence: 97%

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Clinical Pharmacokinetics of Once-Daily Tacrolimus in Solid-Organ Transplant Patients

Staatz

Tett

2015

Clin Pharmacokinet

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Tacrolimus is a pivotal immunosuppressant agent used in solid-organ transplantation. It was originally formulated for oral administration as Prograf(®), a twice-daily immediate-release capsule. In an attempt to improve patient adherence, retain manufacturer market share and/or reduce health care costs, newer once-daily prolonged-release formulations of tacrolimus (Advagraf(®) and Envarsus(®) XR) and various generic versions of Prograf(®) are becoming available. Tacrolimus has a narrow therapeutic index. Small variations in drug exposure due to formulation differences can have a significant impact on patient outcomes. The aim of this review is to critically analyse the published data on the clinical pharmacokinetics of once-daily tacrolimus in solid-organ transplant patients. Forty-three traditional (non-compartmental) and five population pharmacokinetic studies were identified and evaluated. On the basis of the stricter criteria for narrow-therapeutic-index drugs, Prograf(®), Advagraf(®) and Envarsus(®) XR are not bioequivalent [in terms of the area under the concentration-time curve from 0 to 24 h (AUC0-24) or the minimum concentration (C min)]. Patients may require a daily dosage increase if converted from Prograf(®) to Advagraf(®), while a daily dosage reduction appears necessary for conversion from Prograf(®) to Envarsus(®) XR. Prograf(®) itself, or generic immediate-release tacrolimus, can be administered in a once-daily regimen with a lower than double daily dose being reported to give 24-h exposure equivalent to that of a twice-daily regimen. Intense clinical and concentration monitoring is prudent in the first few months after any conversion to once-daily tacrolimus dosing; however, there is no guarantee that therapeutic drug monitoring strategies applicable to one formulation (or twice-daily dosing) will be equally applicable to another. The correlation between the tacrolimus AUC0-24 and C min is variable and not strong for all three formulations, indicating that trough measurements may not always give a good indication of overall drug exposure. Further investigation is required into whether the prolonged-release formulations have reduced within-subject pharmacokinetic variability, which would be a distinct advantage. Whether the effects of factors that influence tacrolimus absorption and pre-systemic metabolism (patient genotype status; gastrointestinal disease and disorders) and drug interactions differ across the formulations needs to be further elucidated. Most pharmacokinetic comparison studies to date have involved relatively stable patients, and many have been sponsored by the pharmaceutical companies manufacturing the new formulations. Larger randomized, controlled trials are needed in different transplant populations to determine whether there are differences in efficacy and toxicity across the formulations and whether formulation conversion is worthwhile in the longer term. While it has been suggested that once-daily administration of tacrolimus may improve patient compliance, further studies a...

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Section: Xrmentioning

confidence: 94%

Section: Xrmentioning

confidence: 97%

Clinical Pharmacokinetics of Once-Daily Tacrolimus in Solid-Organ Transplant Patients

Staatz

Tett

2015

Clin Pharmacokinet

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“…The data regarding conversion from immediate release to prolonged release tacrolimus posttransplant are limited. Although some have found such conversion to be well tolerated and effective [19][20][21][22], others have expressed concern for increased risk of rejection in stable kidney transplant recipients [23]. One study showed that such a conversion may necessitate an increase in the daily dose of Astagraf/ Advagraf by approximately 30% to maintain the target blood trough level unchanged [24].…”

Section: Key Pointsmentioning

confidence: 94%

Extended release once a day tacrolimus

Singh

Visger

Zachariah

2015

Current Opinion in Organ Transplantation

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“…Међутим, показано је да 50% паци-јената након конверзије захтева промену дозе у смислу повећања или смањења оне која је иницијална након конверзије [25][26][27][28][29][30][31] . Због тога, тренутно су у току клиничке студије у којима је иницијална доза при конверзији 70% од дозе пре конверзије 32 .…”

Section: 25unclassified

Comparative pharmacokinetic characteristics of tacrolimus following application of its different pharmaceutical formulations in humans

Rančić¹,

Dragojevic-Simic²

2017

Racion ter

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САЖЕТАКТакролимус је имуносупресивни лек који представља камен темељац у превенцији од-бацивања графта после трансплантације со-лидних органа. Након дугогодишње употребе фармацеутске формулације овог лека која се примењује два пута дневно, уследила је нова ера примене такролимуса са продуженим ос-лобађањем, који се примењује једном дневно. Циљ овог кратког литературног приказа је да се сагледају упоредо фармакокинетске карак-теристике овог лека након његове примене у облику капсула два пута на дан, на 12 сати, и фармацеутске формулације са продуженим ослобађањем, која се дозира једном дневно у здравих особа и пацијената. Међутим, тек бу-дуће клиничке студије ће показати да ли су ове две формулације заиста упоредиве што се тиче фармакокинетских параметара, и, што је још важније, у смислу дуготрајне безбедности такролимуса са продуженим ослобађањем, преживљавања графта и пацијената.Кључне речи: такролимус, фармакокине-тика, трансплантација, фармацеутска форму-лација. ABSTRACTTakrolimus is a cornerstone immunosuppressant in the prevention of solid organ rejection following transplantation. After long-term use of twice daily tacrolimus, a new era of application of extended release tacrolimus for once-daily dosing ensued. The aim of this short communication was to compare pharmacokinetic characteristics of tacrolimus following its application as twice daily drug capsules, each 12 hours, and once-daily capsules with extended release in healthy people and patients. However, only future clinical trials would show whether these two drug formulations are really comparable as far as pharmacokinetic parameters are concerned, and, what is more important, taking into account longterm safety of extended release tacrolimus, survival of grafts and patients themselves.

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Pharmacokinetics in Stable Kidney Transplant Recipients After Conversion From Twice-Daily to Once-daily Tacrolimus Formulations

Abstract: The results of this study provide evidence for safe conversion from Tacrolimus BID to QD with appropriate trough concentration monitoring.

Cited by 46 publications

References 12 publications

Clinical Pharmacokinetics of Once-Daily Tacrolimus in Solid-Organ Transplant Patients

Clinical Pharmacokinetics of Once-Daily Tacrolimus in Solid-Organ Transplant Patients

Extended release once a day tacrolimus

Comparative pharmacokinetic characteristics of tacrolimus following application of its different pharmaceutical formulations in humans

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