Jones C L, Vieth R, Spino M, Ledermann S, Kooh S W, Balfe J, Balfe J W
Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
Clin Nephrol. 1994 Jul;42(1):44-9.
Recent studies in adults have suggested that parenteral 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may have advantages over oral therapy in the management of renal osteodystrophy. The purpose of this study was to determine whether there were clear differences between oral and IP 1,25(OH)2D3 treatments in children who did not pose a treatment problem. Seven children (5 males, 2 females, aged 1.8 to 16 years, median 4.8 years) undergoing peritoneal dialysis were initially treated with oral 1,25(OH)2D3 for a one month equilibration period They were randomly assigned to 3 months of either oral or intraperitoneal (IP) therapy with 1,25(OH)2D3 followed by 3-months-treatment using the alternative route. No significant differences in serum creatinine, phosphate, or parathyroid hormone concentrations were found between the different routes of administration in the patients. No significant differences in height standard deviation scores or renal osteodystrophy scores were found over the six-month study. Paired oral and IP pharmacokinetic studies were performed on these 7 patients and 2 other children who had been treated for at least 2 months using either oral or IP 1,25(OH)2D3. Serum was taken prior to one of the usual 1,25(OH)2D3 doses and 0.5, 1.5, 3, 6, and 24 h afterward. The highest measured concentrations of 1,25(OH)2D3 were found at 1.5 h for both oral and IP treatments (mean Cmax [SD]: oral 116 [23] pmol/l, IP 121 [24] pmol/l, p > 0.05). The AUC's for oral and IP therapy were similar (1701 [276] and 1645 [301] pmol/h/l, respectively). In the paired pharmacokinetic studies no significant differences were found between oral and IP treatments for the serum half life (27.4 [11.6] h and 19.2 [8.1] h, respectively) and total body clearance (15.3 [2.1] h and 18.4 [3.3] h, respectively) of 1,25(OH)2D3. In children who respond appropriately to oral 1,25(OH)2D3 there is no biological advantage to the use of IP 1,25(OH)2D3.
近期针对成年人的研究表明，在治疗肾性骨营养不良方面，肠外注射1,25 - 二羟基维生素D3（1,25[OH]2D3）可能比口服疗法更具优势。本研究的目的是确定对于不存在治疗难题的儿童，口服与腹腔注射1,25(OH)2D3治疗之间是否存在明显差异。7名接受腹膜透析的儿童（5名男性，2名女性，年龄1.8至16岁，中位数4.8岁）最初接受口服1,25(OH)2D3治疗1个月的平衡期，之后随机分配接受为期3个月的口服或腹腔注射（IP）1,25(OH)2D3治疗，然后再用另一种途径治疗3个月。在这些患者中，不同给药途径之间的血清肌酐、磷酸盐或甲状旁腺激素浓度未发现显著差异。在为期6个月的研究中，身高标准差分数或肾性骨营养不良分数也未发现显著差异。对这7名患者以及另外2名已接受口服或腹腔注射1,25(OH)2D3治疗至少2个月的儿童进行了口服和腹腔注射的配对药代动力学研究。在一次常规1,25(OH)2D3剂量给药前以及给药后0.5、1.5、3、6和24小时采集血清。口服和腹腔注射治疗在1.5小时时均测得1,25(OH)2D3的最高浓度（平均Cmax[标准差]：口服116[23]pmol/l，腹腔注射121[24]pmol/l，p>0.05）。口服和腹腔注射治疗的AUC相似（分别为1701[276]和1645[301]pmol/h/l）。在配对药代动力学研究中，口服和腹腔注射治疗在1,25(OH)2D3的血清半衰期（分别为27.4[11.6]小时和19.2[8.1]小时）和全身清除率（分别为15.3[2.1]小时和18.4[3.3]小时）方面未发现显著差异。对于对口服1,25(OH)2D3有适当反应的儿童，使用腹腔注射1,25(OH)2D3并无生物学优势。
