A pharmacokinetic model in the rat and rabbit of the direct measurement of mature bone resorption in vivo with [3H] tetracycline

✍ Scribed by Xiao Qing Li; Cheryl A. Donovan; Leroy Klein

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 718 KB
• Volume: 78
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600781009

✦ Synopsis

This report presents a pharmacokinetic model in the rat and rabbit of the direct quantification of mature bone resorption in vivo. This is based on a first-order reaction rate describing the release of [3H]tetracycline from bone. Compared with the previous method, the model has two new means of expressing bone resorption. First, resorption rate of bone is precisely represented by explicit parameters derived from the model. Second, resorption rate of the whole skeletal system is measured and demonstrated by means of plasma, renal, and bone kinetics of elimination of the isotope. These are represented by the model parameters, the elimination constant, and the half-life of [3H]tetracycline for plasma, urine, and bone. Four ages of normal Sprague Dawley rats and one age of New Zealand white rabbits of both sexes were prelabeled extensively with ["Hltetracycline in utero or during 10 to 84 d of age. Following 1-21 d after the end of prelabeling, the loss of the isotope from femur into plasma and urine was measured at weekly intervals to determine bone resorption of mineral in vivo. The elimination constants of the isotope per day in plasma were -0.148 in weanling rats (4-7 weeks), -0.071 in adolescent rats (1 0-1 4 weeks), and -0.025 in mature rats (15-23 week:;). The urinary elimination constants of the isotope per day were 74, 76, and 76% of those in plasma in weanling, adolescent, and mature rats, respectively. The half-lives of the isotope in the femur were 10 d in neonat;al rats (C-2 weeks), 32 d in weanling rats, 63 d in adolescent rats, and 198 d in mature rats. The different pharmacokinetic parameters lead to the conclusion that bone resorption rates decrease with age between newborn and maturity. The model was also applied to another species (rabbit). The half-life of the isotope was 53 d in femur of 7.5-1 1-week-old !rabbits.