Biomaterial Database

Uptake of alendronate by bone tissue in hypocalcemic and hypercalcemic rats. 1993

J H Lin, and I W Chen, and F A Deluna

Merck Research Laboratories, West Point, PA 19486.

Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate), an antiosteolytic agent, is currently under investigation in the treatment of osteoporosis. Earlier studies in rats from this laboratory have demonstrated that systemically administered alendronate was taken up by bone tissues to the extent of 60-70% of the dose and excreted by the kidneys, 30-40%, and that renal excretion was the only route of elimination of the drug. In this study, a classic three-compartment model was used to determine the kinetics of bone uptake of alendronate in hypo- and hypercalcemic rats. Following intravenous administration (1 mg/kg), the apparent uptake clearance (CL,up) by tibia was approximately 0.18 ml/min/g of bone for control rats, 0.25 ml/min/g for hypocalcemic rats, and 0.05 ml/min/g for hypercalcemic rats. Like other organs, uptake of drugs by bone tissues would be controlled by the plasma flow rate (Q), the fraction of unbound drugs in plasma (fp), and the intrinsic ability of bone uptake (CLin) as described by the equation: CL,up = Q(1 - e-fp.CLin/Q). The plasma flow rate to the tibia of rats was reported to be approximately 0.25 ml/min/g. The unbound fraction of alendronate in plasma of control, hypo-, and hypercalcemic rats was 0.03, 0.45, and 0.035, respectively. By applying the equation, the intrinsic ability (CLin) of bone uptake was estimated to be approximately 10, 2.3, and 1.6 ml/min/g for control, hypo-, and hypercalcemic rats, respectively, indicating that the intrinsic ability of bone to bind alendronate was decreased in both hypo- and hypercalcemic rats.

UI	MeSH Term	Description	Entries
D006996	Hypocalcemia	Reduction of the blood calcium below normal. Manifestations include hyperactive deep tendon reflexes, Chvostek's sign, muscle and abdominal cramps, and carpopedal spasm. (Dorland, 27th ed)	Hypocalcemias
D008297	Male		Males
D010280	Parathyroid Glands	Two pairs of small oval-shaped glands located in the front and the base of the NECK and adjacent to the two lobes of THYROID GLAND. They secrete PARATHYROID HORMONE that regulates the balance of CALCIUM; PHOSPHORUS; and MAGNESIUM in the body.	Gland, Parathyroid,Glands, Parathyroid,Parathyroid Gland
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D001798	Blood Proteins	Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.	Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D001842	Bone and Bones	A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principal cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.	Bone Tissue,Bone and Bone,Bone,Bones,Bones and Bone,Bones and Bone Tissue,Bony Apophyses,Bony Apophysis,Condyle,Apophyses, Bony,Apophysis, Bony,Bone Tissues,Condyles,Tissue, Bone,Tissues, Bone
D004164	Diphosphonates	Organic compounds which contain P-C-P bonds, where P stands for phosphonates or phosphonic acids. These compounds affect calcium metabolism. They inhibit ectopic calcification and slow down bone resorption and bone turnover. Technetium complexes of diphosphonates have been used successfully as bone scanning agents.	Bisphosphonate,Bisphosphonates
D005269	Femur	The longest and largest bone of the skeleton, it is situated between the hip and the knee.	Trochanter,Greater Trochanter,Lesser Trochanter,Femurs,Greater Trochanters,Lesser Trochanters,Trochanter, Greater,Trochanter, Lesser,Trochanters,Trochanters, Greater,Trochanters, Lesser
D006934	Hypercalcemia	Abnormally high level of calcium in the blood.	Milk-Alkali Syndrome,Hypercalcemias,Milk Alkali Syndrome,Syndrome, Milk-Alkali
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia