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Bioavailability and bioequivalence of two oral formulations of alendronate sodium 70 mg: an open-label, randomized, two-period crossover comparison in healthy Korean adult male volunteers.
Clin Ther. 2009 May; 31(5):1037-45.CT

Abstract

BACKGROUND

Alendronate sodium is a Bisphosphonate drug used to treat and prevent osteoporosis and several other bone diseases. A new formulation has been developed and is currently awaiting regulatory approval, pending findings on bioequivalence.

OBJECTIVES

The aims of the present study were to compare the bioavailability and pharmacokinetic (PK) properties, and to determine the bioequivalence, of a test and reference formulation of alendronate sodium 70 mg in a healthy Korean adult male population.

METHODS

This open-label, randomized, 2-sequence, 2-period crossover study was carried out at Hanyang University Medical Center (Seoul, Republic of Korea). Healthy Korean adult male volunteers were randomly assigned to receive a single 70-mg dose of the test or reference formulation of alendronate sodium, administered with 240 mL of water, followed by a 7-day washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Serial blood samples were collected and adverse events were monitored by a clinical investigator via observation, personal interview, and vital signs (blood pressure, heart rate, and body temperature) over a 7-hour period (at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, and 7 hours) after drug administration. Plasma alendronate sodium concentrations were determined using a validated high-performance liquid chromatographic-postcolumn fluorescence derivatization method, with visible detection in the range of 2 to 100 ng/mL and lower limit of quantification set at 2 ng/mL. PK properties, including AUC(0-t), AUC(0-infinity), C(max), T(max), t(1/2), and the elimination constant (k(e)), were determined using non-compartmental analysis. The formulations were considered bioequivalent if the 90% CI ratios for C(max) and AUC were within the predetermined interval of 80% to 125%, the regulatory definition set by the US Food and Drug Administration (FDA).

RESULTS

Twenty-three healthy male volunteers (mean [SD] age, 23.5 [2.0] years [range, 19-28 years]; height, 175.9 [5.4] cm [range, 162.0-185.0 cm]; and weight, 71.2 [9.5] kg [range, 61-96 kg]) were included in the study. No period or sequence effects were detected. The 90% CIs for the corresponding ratios of AUC(0-t), AUC(0-infinity) and C(max) were 84.97 to 114.47, 86.09 to 115.59, and 82.37 to 110.71, respectively. Additionally, the mean (range) of T(max) was 1.09 hours (0.5-2.0 hours), and the mean (SD) of t(1/2) and k(e) were 2.04 (0.97) hours and 0.34 (0.71) hour, respectively. The values for the test and reference formulations were within the FDA bioequivalence definition interval of 80% to 125%. No adverse events were reported in this study.

CONCLUSIONS

Single doses of these formulations of alendronate sodium 70 mg met the criteria for bio-equivalence. No statistically significant differences in AUC(0-t), AUC(0-infinity), and C(max) were found in this healthy Korean adult male population.

Authors+Show Affiliations

Division of Pediatric Surgery, Department of Surgery, College of Medicine, Hanyang University, Seoul, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19539104

Citation

Rhim, Si-Youn, et al. "Bioavailability and Bioequivalence of Two Oral Formulations of Alendronate Sodium 70 Mg: an Open-label, Randomized, Two-period Crossover Comparison in Healthy Korean Adult Male Volunteers." Clinical Therapeutics, vol. 31, no. 5, 2009, pp. 1037-45.
Rhim SY, Park JH, Park YS, et al. Bioavailability and bioequivalence of two oral formulations of alendronate sodium 70 mg: an open-label, randomized, two-period crossover comparison in healthy Korean adult male volunteers. Clin Ther. 2009;31(5):1037-45.
Rhim, S. Y., Park, J. H., Park, Y. S., Lee, M. H., Kim, D. S., Shaw, L. M., Yang, S. C., & Kang, J. S. (2009). Bioavailability and bioequivalence of two oral formulations of alendronate sodium 70 mg: an open-label, randomized, two-period crossover comparison in healthy Korean adult male volunteers. Clinical Therapeutics, 31(5), 1037-45. https://doi.org/10.1016/j.clinthera.2009.05.001
Rhim SY, et al. Bioavailability and Bioequivalence of Two Oral Formulations of Alendronate Sodium 70 Mg: an Open-label, Randomized, Two-period Crossover Comparison in Healthy Korean Adult Male Volunteers. Clin Ther. 2009;31(5):1037-45. PubMed PMID: 19539104.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bioavailability and bioequivalence of two oral formulations of alendronate sodium 70 mg: an open-label, randomized, two-period crossover comparison in healthy Korean adult male volunteers. AU - Rhim,Si-Youn, AU - Park,Jin-Hee, AU - Park,Yoo-Sin, AU - Lee,Min-Ho, AU - Kim,Dong-Sun, AU - Shaw,Leslie M, AU - Yang,Seok-Chul, AU - Kang,Ju-Seop, PY - 2009/03/11/accepted PY - 2009/6/23/entrez PY - 2009/6/23/pubmed PY - 2009/8/29/medline SP - 1037 EP - 45 JF - Clinical therapeutics JO - Clin Ther VL - 31 IS - 5 N2 - BACKGROUND: Alendronate sodium is a Bisphosphonate drug used to treat and prevent osteoporosis and several other bone diseases. A new formulation has been developed and is currently awaiting regulatory approval, pending findings on bioequivalence. OBJECTIVES: The aims of the present study were to compare the bioavailability and pharmacokinetic (PK) properties, and to determine the bioequivalence, of a test and reference formulation of alendronate sodium 70 mg in a healthy Korean adult male population. METHODS: This open-label, randomized, 2-sequence, 2-period crossover study was carried out at Hanyang University Medical Center (Seoul, Republic of Korea). Healthy Korean adult male volunteers were randomly assigned to receive a single 70-mg dose of the test or reference formulation of alendronate sodium, administered with 240 mL of water, followed by a 7-day washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Serial blood samples were collected and adverse events were monitored by a clinical investigator via observation, personal interview, and vital signs (blood pressure, heart rate, and body temperature) over a 7-hour period (at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, and 7 hours) after drug administration. Plasma alendronate sodium concentrations were determined using a validated high-performance liquid chromatographic-postcolumn fluorescence derivatization method, with visible detection in the range of 2 to 100 ng/mL and lower limit of quantification set at 2 ng/mL. PK properties, including AUC(0-t), AUC(0-infinity), C(max), T(max), t(1/2), and the elimination constant (k(e)), were determined using non-compartmental analysis. The formulations were considered bioequivalent if the 90% CI ratios for C(max) and AUC were within the predetermined interval of 80% to 125%, the regulatory definition set by the US Food and Drug Administration (FDA). RESULTS: Twenty-three healthy male volunteers (mean [SD] age, 23.5 [2.0] years [range, 19-28 years]; height, 175.9 [5.4] cm [range, 162.0-185.0 cm]; and weight, 71.2 [9.5] kg [range, 61-96 kg]) were included in the study. No period or sequence effects were detected. The 90% CIs for the corresponding ratios of AUC(0-t), AUC(0-infinity) and C(max) were 84.97 to 114.47, 86.09 to 115.59, and 82.37 to 110.71, respectively. Additionally, the mean (range) of T(max) was 1.09 hours (0.5-2.0 hours), and the mean (SD) of t(1/2) and k(e) were 2.04 (0.97) hours and 0.34 (0.71) hour, respectively. The values for the test and reference formulations were within the FDA bioequivalence definition interval of 80% to 125%. No adverse events were reported in this study. CONCLUSIONS: Single doses of these formulations of alendronate sodium 70 mg met the criteria for bio-equivalence. No statistically significant differences in AUC(0-t), AUC(0-infinity), and C(max) were found in this healthy Korean adult male population. SN - 0149-2918 UR - https://www.unboundmedicine.com/medline/citation/19539104/Bioavailability_and_bioequivalence_of_two_oral_formulations_of_alendronate_sodium_70_mg:_an_open_label_randomized_two_period_crossover_comparison_in_healthy_Korean_adult_male_volunteers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(09)00147-7 DB - PRIME DP - Unbound Medicine ER -