An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis

Pediatric Nephrology : Journal of the International Pediatric Nephrology Association
Winnie Y SohnBradley A Warady

Abstract

Calcimimetics, shown to control biochemical parameters of secondary hyperparathyroidism (SHPT), have well-established safety and pharmacokinetic profiles in adult end-stage renal disease subjects treated with dialysis; however, such studies are limited in pediatric subjects. In this study, the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cinacalcet were evaluated in children with chronic kidney disease (CKD) and SHPT receiving dialysis. Twelve subjects received a single dose of cinacalcet (0.25 mg/kg) orally or by nasogastric or gastric tube. Subjects were randomized to one of two parathyroid hormone (PTH) and serum calcium sampling sequences: [(1) 2, 8, 48 h; or (2) 2, 12, 48 h] and assessed for 72 h after dosing. Median plasma cinacalcet tmax was 1 h (range 0.5-4.0 h); mean (SD) Cmax and AUClast were 2.83 (1.98) ng/mL and 11.8 (8.74) h*ng/mL, respectively; mean (SD) half-life (t1/2) was 3.70 (2.57) h. Dose adjustments, based upon body weight (mg/kg), minimized the effects of age, body weight, body surface area, and body mass index on cinacalcet PK. Reductions in serum PTH levels from baseline were observed at 2 to 8 h post-dose (median 10.8 and 29.6%, respectively), returned towards baseline by 12...Continue Reading

References

Sep 22, 1999·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·B D Kuizon, I B Salusky
May 18, 2000·The New England Journal of Medicine·W G GoodmanI B Salusky
Dec 11, 2002·Kidney International·Jaap W GroothoffFriedo W Dekker
Apr 9, 2004·The New England Journal of Medicine·Geoffrey A BlockWilliam G Goodman
May 20, 2008·Primary Care·Sharon M Moe
May 28, 2008·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Jutta MuscheitesDieter Haffner
Jun 5, 2008·The Journal of Clinical Endocrinology and Metabolism·Julie Ann SosaSanziana A Roman
Jul 2, 2009·Clinical Pharmacokinetics·Desmond Padhi, Robert Harris
Oct 20, 2009·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Caroline PlattMoin A Saleem
Apr 2, 2011·Clinical Journal of the American Society of Nephrology : CJASN·John CunninghamMariano Rodriguez
Sep 29, 2011·Nature Reviews. Nephrology·Claus Peter Schmitt, Otto Mehls
Nov 5, 2011·Clinical Journal of the American Society of Nephrology : CJASN·Katherine Wesseling-PerryIsidro B Salusky
May 29, 2012·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Desmond PadhiEdward Posvar
Mar 8, 2013·Seminars in Nephrology·Katherine Wesseling-Perry, Isidro B Salusky
Jun 17, 2014·Seminars in Pediatric Surgery·Jocelyn F BurkeAnkush Gosain
Aug 30, 2014·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Nadine M KhouzamIsidro B Salusky
Sep 17, 2014·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·P EvenepoelS Yue
Dec 10, 2014·The Cochrane Database of Systematic Reviews·Angela E BallingerGiovanni F M Strippoli
Jul 4, 2015·Journal of the American Society of Nephrology : JASN·Michelle R DenburgMary B Leonard
Aug 27, 2016·Clinical Journal of the American Society of Nephrology : CJASN·Anthony A PortaleIsidro B Salusky

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Citations

Nov 7, 2019·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Justine Bacchetta
Nov 2, 2019·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Louise McAlisterRukshana Shroff
Oct 24, 2019·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Justine BacchettaUNKNOWN European Society for Paediatric Nephrology and the Chronic Kidney Disease-Mineral and Bone Disorders and Dialysis Working Gr
May 6, 2020·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Julie BernardorJustine Bacchetta
May 6, 2020·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Bradley A WaradyJustine Bacchetta

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