Chalitpon Na nakorn, Narubodee Phadungsombut, Thitima Chuchome, and Kamonthip Wiwattanawongsa

pp. 325 - 331

Abstract

Alendronate is indicated for treatment of a variety of bone metabolism disorders. In spite of quite low plasma concentrations following oral administration, pharmacokinetic study of alendronate based on plasma concentrations had normally
been reported for up to 8 h. Due to much longer detectable periods in urine, a number of pharmacokinetic studies have been
based upon urinary excretion data. The objective of this study was to determine pharmacokinetics of alendronate following
oral administration of combined Alendronate/Vitamin D₃
 tablet. Blood and urine samples were collected for 10 h after oral
administration of a combined Alendronate/Vitamin D₃
 tablet to healthy volunteers. Alendronate levels in plasma and urine
samples were determined by high-performance liquid chromatography (HPLC) with fluorescence detection. The analytical
method involved co-precipitation of alendronate in plasma or urine samples with calcium and followed by solid-phase extraction (SPE) process. Pharmacokinetic parameters were analyzed by the non-compartmental method using WinNonlin. Pharmacokinetics parameters, i.e. C_max
, T_max
, AUC_0-10, T_1/2, were 56.6±11.8 ng/mL, 1.29±0.39 h, 132.4±46.9 ng·h/mL, and 3.43±2.24 h,
respectively. Amount excreted in 10 h urine and maximum excretion rate (R_max
) were 578.59±308.9 µg and 143.3±72.8 µg/h,
respectively. Although these parameters were different from previously reported values, R_max
 obtained at 1.29±0.76 h agreed
well with T_max
 observed from plasma data. Based upon urinary excretion data, enhanced absorption of alendronate after
administration of a combined Alendronate/Vitamin D₃
 tablet is suggested.