Pharmacokinetics of sulfobutylether- -cyclodextrin (SBECD) in subjects on hemodialysis

Luke, David R.; Wood, Nolan; Tomaszewski, Konrad E.; Damle, Bharat

doi:10.1093/ndt/gfr472

Cited by 52 publications

(38 citation statements)

References 11 publications

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“…These observations are consistent with previous reports on dialysis of SBECD. From a model of SBECD pharmacokinetics in ESRD subjects receiving IV voriconazole every 12 hours, it was predicted that hemodialysis (2‐ to 6‐hour sessions) would remove on average 46% of the total systemic load of SBECD . No adverse events in this study were attributed to SBECD.…”

Section: Discussionmentioning

confidence: 79%

Clinical Pharmacokinetics of Sulfobutylether‐β‐Cyclodextrin in Patients With Varying Degrees of Renal Impairment

Hoover¹,

Alcorn

Lawrence

et al. 2018

The Journal of Clinical Pharma

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Delafloxacin, a fluoroquinolone, has activity against Gram-positive organisms including methicillin-resistant S aureus and fluoroquinolone-susceptible and -resistant Gram-negative organisms. The intravenous formulation of delafloxacin contains the excipient sulfobutylether-β-cyclodextrin (SBECD), which is eliminated by renal filtration. This study examined the pharmacokinetics and safety of SBECD after single intravenous (IV) infusions in subjects with renal impairment. The study was an open-label, parallel-group, crossover study in subjects with normal renal function or mild, moderate, or severe renal impairment, and those with end-stage renal disease undergoing hemodialysis. Subjects received 300 mg delafloxacin IV or placebo IV, containing 2400 mg SBECD, in 2 periods separated by ≥14-day washouts. SBECD total clearance decreased with decreasing renal function, with a corresponding increase in area under the concentration-time curve (AUC ). After IV delafloxacin 300 mg administration, SBECD mean total clearance was 6.28 and 1.24 L/h, mean AUC was 387 and 2130 h·μg/mL, and mean renal clearance was 5.36 and 1.14 L/h in normal and severe renal subjects, respectively. Similar values were obtained after IV placebo administration. In subjects with end-stage renal disease, delafloxacin 300 mg IV produced mean SBECD AUC values of 2715 and 7861 h·μg/mL when dosed before and after hemodialysis, respectively. Total SBECD clearance exhibited linear relationships to estimated glomerular filtration rate and creatinine clearance. Single doses of IV delafloxacin 300 mg and IV placebo were well tolerated in all groups. In conclusion, decreasing renal function causes reduced SBECD clearance and increased exposures, but SBECD continues to exhibit a good safety and tolerability profile in IV formulations.

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Section: Discussionmentioning

confidence: 79%

Clinical Pharmacokinetics of Sulfobutylether‐β‐Cyclodextrin in Patients With Varying Degrees of Renal Impairment

Hoover¹,

Alcorn

Lawrence

et al. 2018

The Journal of Clinical Pharma

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“…However, most previous studies used parent cyclodextrins, notably α‐cyclodextrin, β‐cyclodextrin or methylated β‐cyclodextrin. It has been shown that SBECD, a rationally designed β‐cyclodextrin derivative, has a more favourable toxicological profile compared to the parent cyclodextrins . Although intravenous SBECD causes vacuolation of renal tubules in a dose‐dependent manner in animal models, SBECD‐induced vacuolation of renal tubules is not associated with alteration of renal function and is reversible following cessation of treatment .…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that SBECD, a rationally designed b-cyclodextrin derivative, has a more favourable toxicological profile compared to the parent cyclodextrins. 9,33,34 Although intravenous SBECD causes vacuolation of renal tubules in a dosedependent manner in animal models, SBECD-induced vacuolation of renal tubules is not associated with alteration of renal function and is reversible following cessation of treatment. 9,35 In fact, there are several studies that demonstrate no correlation between the SBECD exposure and deterioration of renal function in patients with compromised renal function.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic drug monitoring and safety of intravenous voriconazole formulated with sulfobutylether β‐cyclodextrin in haematological patients with renal impairment

Kim

Kwon

Park

et al. 2016

Mycoses

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SummaryBecause of concerns about accumulation of cyclodextrin, oral voriconazole is recommended for patients with renal impairment. However, intravenous voriconazole may occasionally be imperative in critically ill patients with life-threatening invasive aspergillosis. We investigated the clinical effects of intravenous voriconazole formulated with sulfobutylether b-cyclodextrin (SBECD) in patients with renal impairment. A prospective observational study was conducted on 25 adult patients with haematological malignancies who were treated with intravenous voriconazole for invasive aspergillosis. Among them, seven patients had a baseline creatinine clearance (CrCl) <50 ml min À1 (case). Although voriconazole trough concentrations were significantly higher in cases (5.84 mg l À1 ) than controls (2.28 mg l À1 ), the proportion of concentrations within the target range did not differ between two groups (4/7 and 12/18, respectively; P = 0.658). The frequency of severe adverse events in cases (3/7) was comparable to that of controls (4/18; P = 0.355). No patients showed significant deterioration in renal function after the voriconazole therapy even in patients with renal impairment. Although CrCl <50 ml min À1 was associated with higher voriconazole concentrations, its clinical impact remains unclear. SBECD-formulated intravenous voriconazole did not lead to a higher incidence of severe adverse events including nephrotoxicity in haematological patients with CrCl <50 ml min À1 .

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“…9 Although SBECD has been shown to be eliminated in dialysate, it does accumulate to a greater extent than delafloxacin. [10][11][12] Product labeling for delafloxacin recommends an IV dose reduction for patients with severe renal impairment from 300 mg every 12 hours (Q12h) to 200 mg Q12h due to the presence of SBECD in the formulation, with no change in the recommended oral dose of 450 mg Q12h. 1 Delafloxacin in its present IV formulation containing SBECD does not have dosing recommendations for patients with ESRD.…”

mentioning

confidence: 99%

Pharmacokinetics of Intravenous Delafloxacin in Patients With End‐Stage Renal Disease

Hoover¹,

Alcorn

Lawrence

et al. 2018

The Journal of Clinical Pharma

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This was an open-label, parallel-group, crossover study that examined the pharmacokinetics and safety of delafloxacin, an anionic fluoroquinolone, after a single intravenous infusion in subjects with end-stage renal disease (ESRD; creatinine clearance <15 mL/min) undergoing hemodialysis compared with healthy subjects. Subjects received 300 mg delafloxacin containing sulfobutylether-β-cyclodextrin in 2 periods separated by ≥14-day washouts. Blood and urine samples were collected, and pharmacokinetic parameters were calculated using noncompartmental methods. The mean total exposure (area under the curve) of delafloxacin was about 2.1 and 2.6 higher for subjects with ESRD compared to healthy subjects when dosed 1 hour before or 1 hour after hemodialysis, respectively. Compared to subjects with normal renal function, the maximum exposure to delafloxacin was 13% and 33% higher for ESRD subjects given delafloxacin 1 hour before and 1 hour after hemodialysis, respectively. The mean clearance was 13.7 L/h for healthy subjects and was lower for subjects with ESRD when given before (7.39 L/h) or after (5.69 L/h) hemodialysis. The clearance of delafloxacin in dialysate was 4.74 L/h with about 19.2% of the delafloxacin dose recovered after a 4-hour dialysis session. Delafloxacin was well tolerated in both healthy and ESRD subjects, with diarrhea being the most reported treatment-emergent adverse event.

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Pharmacokinetics of sulfobutylether- -cyclodextrin (SBECD) in subjects on hemodialysis

Abstract: Hemodialysis can significantly reduce levels of SBECD in subjects with end-stage renal disease.

Cited by 52 publications

References 11 publications

Clinical Pharmacokinetics of Sulfobutylether‐β‐Cyclodextrin in Patients With Varying Degrees of Renal Impairment

Clinical Pharmacokinetics of Sulfobutylether‐β‐Cyclodextrin in Patients With Varying Degrees of Renal Impairment

Therapeutic drug monitoring and safety of intravenous voriconazole formulated with sulfobutylether β‐cyclodextrin in haematological patients with renal impairment

Pharmacokinetics of Intravenous Delafloxacin in Patients With End‐Stage Renal Disease

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