Richards A, Kragstrup J, Nielsen-Kudsk F
J Dent Res. 1985 Mar;64(3):425-30. doi: 10.1177/00220345850640030601.
The present study was undertaken to estimate bio-availability and biological half-life of fluoride and accumulation of fluoride in bone in the domestic pig. Eight animals receiving 2 mg F-/kg b.w. per day from age 8 to 14 months were compared with eight controls. Plasma fluoride concentrations just prior to the daily oral dose were measured at regular intervals. After 112 days post-dose, plasma fluoride levels were measured over a 48-hour period following the daily oral dose or a single intravenous dose. Mean bio-availability factor for the oral dose was 0.3 (range 0.2-0.4), and mean biological half-life was 59 days (range 49-72). Bone fluoride content calculated from the pharmacokinetic parameters derived from plasma data was similar to the content of fluoride measured in the bone at slaughter. The study showed that accumulation of fluoride in bone influences plasma fluoride levels during chronic administration of fluoride to growing pigs. The long biological half-life found showed that it was not possible to achieve steady-state plasma levels within the six-month experimental period used. This means that, for dose-response studies of dental fluorosis in this animal, it is not possible to achieve steady-state plasma concentrations as a basis for correlations to the degrees of pathological change observed in the teeth.
本研究旨在评估家猪体内氟化物的生物利用度和生物半衰期,以及氟化物在骨骼中的蓄积情况。将8只8至14月龄每天接受2毫克氟/千克体重氟化物的动物与8只对照动物进行比较。定期测量每日口服剂量前的血浆氟化物浓度。给药后112天,在每日口服剂量或单次静脉注射后的48小时内测量血浆氟化物水平。口服剂量的平均生物利用度因子为0.3(范围为0.2 - 0.4),平均生物半衰期为59天(范围为49 - 72天)。根据血浆数据推导的药代动力学参数计算出的骨骼氟含量与屠宰时骨骼中测得的氟含量相似。该研究表明,在向生长猪长期施用氟化物的过程中,骨骼中氟化物的蓄积会影响血浆氟化物水平。所发现的较长生物半衰期表明,在为期6个月的实验期内无法达到稳态血浆水平。这意味着,对于该动物氟斑牙的剂量反应研究,不可能达到稳态血浆浓度作为与牙齿中观察到的病理变化程度相关性的基础。