title: Chronotherapy of high-dose active vitamin D3 in haemodialysis patients with secondary hyperparathyroidsm: a repeated dosing study.
abstract: OBJECTIVE
  Renal osteodystrophy is the major complication in patients with end-stage renal failure. Oral or intravenous vitamin D3 (D3) is given to these patients, but severe hypercalcaemia sometimes interrupts this therapy. This study was undertaken to determine whether the effectiveness and safety of D3 also depend on its dosing time during a repeated treatment.
  
  
  METHODS
  A higher dose (3 micro g) was given orally to 13 haemodialysis patients at 08.00 h or 20.00 h for 12 months by a randomized, cross-over design.
  
  
  RESULTS
  Three patients were withdrawn due to severe hypercalcaemia after switching from 08.00 h to 20.00 h dosings. The elevation in serum calcium concentration was significantly (P < 0.001) greater during the 08.00 h dosing in the remaining ten patients. Mean serum Ca concentration after the trial was 10.92 (95% confidence interval (CI) 10.79, 11.06) and 9.55 mg dl-1 (95% CI 9.30, 9.71) by 08.00 h and 20.00 h dosing, respectively. On the other hand, the suppression of the elevated serum parathyroid hormone (PTH) and subsequent increment in bone density were significantly greater during the 08.00 h dosing. Mean PTH concentration after the trial was 414 (95% CI 360, 475) and 220 pg ml-1 (95% CI 202, 249) by 08.00 h and 20.00 h dosing, respectively (P = 0.02). Mean increment of bone density after the trial was 22 (95% CI 8, 32) and 57 g cm-3 (95% CI 43, 83) by 08.00 h and 20.00 h dosing, respectively (P = 0.04).
  
  
  CONCLUSIONS
  These results indicate that a higher dose of oral D3 is more effective and safe after dosing at evening in patients with renal osteodystrophy.
authors.affiliation: Department of Clinical Pharmacology, Jichi Medical School, Minamikawachi, Tochigi, and Haemodialysis Unit, Moka Hospital, Moka, Tochigi, Japan. tsuru@jichi.ac.jp
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsuruoka
authors.forename: Michi
authors.initials: M
authors.lastname: Wakaumi
authors.forename: Koichi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Saito
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002762:Cholecalciferol / Q000008:administration & dosage*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000517:prevention & control; D019454:Chronotherapy / Q000379:methods; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000517:prevention & control; D006962:Hyperparathyroidism, Secondary / Q000150:complications*; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000379:methods*
chemical_list: D002762:Cholecalciferol