Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Belatacept in Renal Transplant Patients

Shen, Jim X.; Block, A. Jay; Townsend, Robert M.; You, Xiaoli; Shen, Yun; Zhou, Shi‐Ping; Geng, Deqin; McGirr, N.; Soucek, K; Pursley, Janice; Russo, G.; Kaul, Sanjeev

doi:10.1097/00007890-201007272-00785

Cited by 6 publications

(5 citation statements)

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“…At day 5 and weeks 2, 4, 12, 24, and 52, the mean preinfusion CD86 saturations were 94%, 88%, 86%, 75%, 67%, and 65%, respectively. 17 These data are consistent with the decreasing frequency of belatacept administrations during these time points.…”

Section: Pharmacodynamicssupporting

confidence: 82%

“…Kidney transplant recipients receiving the more intensive belatacept regimen demonstrated concentration dependence for the CD86 receptor, which was nearly fully saturated by day 5 (minimum saturation ~94%). 17 Belatacept demonstrated a declining trend in CD86 saturation. At day 5 and weeks 2, 4, 12, 24, and 52, the mean preinfusion CD86 saturations were 94%, 88%, 86%, 75%, 67%, and 65%, respectively.…”

Section: Pharmacodynamicsmentioning

confidence: 98%

“…16 Belatacept showed minimal systemic accumulation during steady-state in de novo kidney transplant recipients during the maintenance phase. The terminal half-life of belatacept in de novo kidney transplant recipients was approximately 8-10 days, 16,17 allowing for prolonged intervals between administrations. Demographic parameters such as age, race, and sex have not been shown to alter the pharmacokinetic parameters.…”

Section: Pharmacokineticsmentioning

confidence: 99%

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Belatacept Post Kidney Transplantation

Bajjoka¹,

Makowski

Churchill

et al. 2012

Journal of Pharmacy Technology

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Objective: To review the use of belatacept as an alternative to calcineurin inhibitor-based regimens for maintenance immunosuppression in renal transplant recipients. Data Sources:To provide an extensive overview of the pharmacology, pharmacokinetics, efficacy, and safety of belatacept, a MEDLINE/PubMed search (1980( -December 2011 was performed for all articles evaluating belatacept's properties and patient outcomes, as well as abstracts from recent meetings, using key words belatacept, pharmacology, efficacy, pharmacokinetics, and safety.Study Selection/Data Extraction: Phase 2 and 3 studies in humans describing use, adverse reactions, pharmacology, pharmacokinetics, efficacy, and safety of belatacept were identified and reviewed. Other articles were identified through PubMed.Data Synthesis: Belatacept, a costimulation blocker, is a biologic recombinant fusion protein that has been shown to prevent acute cellular rejection in kidney transplant recipients and preserve renal function. It was recently approved by the FDA as an antirejection immunosuppressant agent for use in kidney transplant recipients. It is the first biologic agent used for maintenance immunosuppression. It acts as an antagonist to CD80 and CD86 receptors located on the surface of antigen presenting cells, thereby blocking CD28 T-cell activation and, thus, preventing acute rejection. In comparison with patients receiving other current therapies, patients on belatacept have demonstrated superior renal function with comparable outcomes in patient and graft survival. Conclusions:Belatacept has potential for use as an alternative to current maintenance immunosuppression regimens, with potentially fewer adverse effects.

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Section: Pharmacodynamicssupporting

confidence: 82%

Section: Pharmacodynamicsmentioning

confidence: 98%

Section: Pharmacokineticsmentioning

confidence: 99%

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Belatacept Post Kidney Transplantation

Bajjoka¹,

Makowski

Churchill

et al. 2012

Journal of Pharmacy Technology

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“…The belatacept MI regimen delivers approximately twice the exposure (time‐averaged concentration) to belatacept than the LI regimen between months 2 and 7, 15 and the associations between belatacept exposure and the safety end points of serious infection and CNS events suggest that the increased exposure delivered by the MI regimen between months 2 and 7 may increase the safety risk of these adverse events. The results of the E–R and exposure–safety analyses were consistent with clinical safety results.…”

Section: Discussionmentioning

confidence: 99%

Time-Varying Belatacept Exposure and Its Relationship to Efficacy/Safety Responses in Kidney-Transplant Recipients

Zhou

Shen

Yang

et al. 2012

Clin Pharmacol Ther

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Belatacept is the first T-cell costimulation blocker to be approved for the prophylaxis of organ rejection in adult kidney-transplant recipients (KTRs) and represents an alternative to calcineurin inhibitors, which are known to be nephrotoxic. After transplant, the risk of acute rejection (AR) decreases with time. Accordingly, belatacept exposures were reduced over time by changes in dose and dosing interval in the two treatment regimens tested in two phase III studies. Time-varying belatacept exposures were characterized by developing and applying a population pharmacokinetic model. Clearance and volume of central and peripheral compartments increased with baseline body weight, but there was no effect of age, gender, race, renal/hepatic function, diabetes, patient type (healthy/KTR), or dialysis on belatacept clearance. Exposure-response analyses showed that lower exposures did not compromise efficacy (as measured by AR), whereas higher exposures were associated with increased serious infections and central nervous system events.

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“…The coefficient variability of PK parameters was approximately 20 --30%. The half-life was approximately 8 --10 days [25].…”

Section: Pharmacokineticsmentioning

confidence: 99%

Belatacept: a new biological agent for maintenance immunosuppression in kidney transplantation

Arora¹,

Tangirala²,

Osadchuk³

et al. 2012

Expert Opinion on Biological Therapy

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Despite the increased incidence and severity of acute rejection with belatacept in Phase II and III studies, a better preservation of GFR and reduced incidence of chronic allograft nephropathy was observed as compared with CNIs. Patient and graft survivals were similar over 3- and 5-year follow-up post-transplantation. Incidence of adverse events were similar between the groups, but the risk of post-transplant lymphoproliferative disorder, predominantly involving CNS, was higher in Epstein-Barr virus seronegative recipients on belatacept, especially with a more intensive regimen. CV and metabolic end points were more favorable in belatacept versus CNI groups with similar incidences of diabetes after transplantation. Belatacept seems to be a promising drug for the future, but long-term outcomes are awaited.

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Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Belatacept in Renal Transplant Patients

Cited by 6 publications

References 0 publications

Belatacept Post Kidney Transplantation

Belatacept Post Kidney Transplantation

Time-Varying Belatacept Exposure and Its Relationship to Efficacy/Safety Responses in Kidney-Transplant Recipients

Belatacept: a new biological agent for maintenance immunosuppression in kidney transplantation

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