Joffe P, Ladefoged S D, Cintin C, Jensen L T, Hyldstrup L
Department of Nephrology, Herlev County Hospital, University of Copenhagen, Denmark.
Nephrol Dial Transplant. 1994;9(5):524-31. doi: 10.1093/ndt/9.5.524.
To study the acute effect of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) on serum levels of alkaline phosphatase, Ca2+, osteocalcin, parathyroid hormone (PTH), phosphate and type I and III procollagens (PICP and PIIINP respectively) in patients undergoing peritoneal dialysis. Also, 1,25-(OH)2D3 was measured.
Single doses of 1 alpha-OHD3 (80 ng/kg body wt) were given in randomized cross-over fashion, orally, intraperitoneally (i.p.) and intravenously (i.v.) on three occasions. Blood was sampled at 0, 1, 6, 12, and 24 h after administration of 1 alpha-OHD3.
Following oral administration of 1 alpha-OHD3, a decrease in serum alkaline phosphatase was seen when levels at 1 and 6 h were compared to baseline (P < 0.05). Oral and i.v. drug administrations resulted in an increasing trend in serum Ca2+ throughout the study (P < 0.05). Moreover, a difference in serum Ca2+ was found when 24-h levels after oral 1 alpha-OHD3 dose was compared to baseline (P < 0.05). Serum osteocalcin at 12 and 24 h after oral 1 alpha-OHD3 compared to baseline were increased (P < 0.05). Intact PTH followed a circadian rhythm after all three routes of drug delivery. After 24 h, significant decreases of intact PTH were observed in the oral and i.v. group. No changes in serum phosphate and serum PICP levels were observed over time after oral, i.p., and i.v. delivery of 1 alpha-OHD3. However, serum PIIINP following oral and i.p. administration of 1 alpha-OHD3 decreased at 1 and 6 h (P < 0.05).
Oral and i.v. administration of 1 alpha-OHD3 does influence serum levels of osteocalcin, PTH, and PIIINP: Noticeable is the significant increase in serum osteocalcin after oral administration of 1 alpha-OHD3, the remarkable increase (22.6%) in osteocalcin 24 h after i.v. 1 alpha-OHD3, though not statistically significant, the increase in serum PTH levels 12 h following oral and i.v. doses of 1 alpha-OHD3 and the moderate effect on serum Ca2+ levels.
研究1α-羟基胆钙化醇(1α-OHD3)对腹膜透析患者血清碱性磷酸酶、钙离子、骨钙素、甲状旁腺激素(PTH)、磷酸盐以及Ⅰ型和Ⅲ型前胶原(分别为PICP和PIIINP)水平的急性影响。同时,检测1,25-(OH)2D3。
以随机交叉方式分三次口服、腹腔内(i.p.)和静脉内(i.v.)给予单剂量的1α-OHD3(80 ng/kg体重)。在给予1α-OHD3后0、1、6、12和24小时采集血样。
口服1α-OHD3后,将1小时和6小时的水平与基线水平比较时,血清碱性磷酸酶降低(P < 0.05)。在整个研究过程中,口服和静脉给药导致血清钙离子呈上升趋势(P < 0.05)。此外,将口服1α-OHD3剂量后24小时的水平与基线水平比较时,发现血清钙离子存在差异(P < 0.05)。口服1α-OHD3后12小时和24小时的血清骨钙素与基线相比升高(P < 0.05)。在所有三种给药途径后,完整PTH呈现昼夜节律。24小时后,在口服和静脉给药组中观察到完整PTH显著降低。在口服、腹腔内和静脉内给予1α-OHD3后,随着时间推移,血清磷酸盐和血清PICP水平未观察到变化。然而,口服和腹腔内给予1α-OHD3后,血清PIIINP在1小时和6小时降低(P < 0.05)。
口服和静脉内给予1α-OHD3确实会影响血清骨钙素、PTH和PIIINP水平:值得注意的是,口服1α-OHD3后血清骨钙素显著增加,静脉内给予1α-OHD3后24小时骨钙素显著增加(22.6%),尽管无统计学意义,口服和静脉内给予1α-OHD3后12小时血清PTH水平增加,以及对血清钙离子水平有中等程度影响。