A simple pharmacokinetic model of alendronate developed using plasma concentration and urine excretion data from healthy men

Abstract

The study of pharmacokinetics of alendronate has been hampered by difficulties in accurately and reproducibly determining their concentrations in serum and urine. Thus, pharmacokinetic characteristics of alendronate have been described in many reports based on urinary excretion data; and plasma pharmacokinetics and the simultaneous pharmacokinetic models of alendronate in plasma and urine are not available. The aims of this study were to measure alendronate concentration in plasma and excretion in urine concurrently and to develop compartmental pharmacokinetic model using urine data. In open-label, single-dose pharmacokinetic study, 10 healthy male volunteers received oral dose of alendronate (70 mg tablet). Blood and urine alendronate concentrations were determined using validated high-performance liquid chromatography method. Non-compartmental analysis was performed using WinNonlin program (Pharsight Inc., Apex, NC). A one-compartment pharmacokinetic model was applied to describe pharmacokinetics of alendronate. A peak plasma alendronate concentration of 33.10 ± 14.32 ng/mL was attained after 1.00 ± 0.16 h. The cumulative amount of alendronate excreted in urine and peak excretion rate were 731.28 ± 654.57 μg and 314.68 ± 395.43 μg/h, respectively. The model, which included first-order absorption rate for oral dosing, showed good fit to alendronate data obtained from plasma and urine. The absorption rate constant was 2.68 ± 0.95 h(-1). The elimination rate constants Kurine and Knon-ur were 0.005 ± 0.004 h(-1) and 0.42 ± 0.08 h(-1), respectively. The pharmacokinetics of alendronate in plasma and urine of healthy men can be predicted using one-compartment model, and thus the behavior of drug in plasma can be estimated from urinary excretion data.

Alteration of macrophage viability, differentiation, and function by bisphosphonates

“…After administration, BPs distribute in plasma and consequently retain in the bone by approximately 60% (Chae et al., ; Chen et al., ; Khan et al., ; Kozloff et al., ; Sato et al., ). In the mandible, BP deposits on the alveolar bone and bone surrounding the periodontal ligament of molar roots (Kozloff et al., ).…”

“…After administration, BPs distribute in plasma and consequently retain in the bone by approximately 60% (Chae et al, 2014;Chen et al, 2002;Khan et al, 1997;Kozloff et al, 2010;Sato et al, 1991).…”

“…After administration of BP, most of the drug is plasma‐bound. About 40% of the dose is excreted in the urine within 24 hr, and the remainder of the dose is presumed to be bound to the bone (Chae et al., ; Chen et al., ; Khan et al., ). This suggests that several cells could likely expose to BP ranging from immune cells circulating in the blood to cells residing in the bone.…”

Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study

“…We selected urine sampling times based on previously published urinary excretion data for rifampin, and chose a time point for evaluation in the validation study based on diagnostic accuracy in healthy subjects. In future work we will employ optimal sampling theory to identify urine sampling schemes that predict serum pharmacokinetics better than a single 4-h timed void [ 24 ].…”

Mechanistic PK-PD model of alendronate treatment of postmenopausal osteoporosis predicts bone site-specific response

“…Little is known about urinary excretion in long term, and only the experimental Frontiers in Bioengineering and Biotechnology frontiersin.org data obtained by Khan et al (1997) could be found to validate these specific results. The experimental data from Chae et al (2014) were used to adjust the serum concentration in short term, while those obtained by Kang et al (2006) were used for the short-term urinary excretion. Other authors measured similar values for both types of results (Cocquyt et al, 1999;Acotto et al, 2012).…”