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

Rhim, Si-Youn; Park, Jin Hee; Park, Yoo-Sin; Kim, Dong–Sun; Shaw, Leslie M.; Yang, Seung Won; Kang, Ju‐Seop

doi:10.1016/j.clinthera.2009.05.001

Cited by 16 publications

(13 citation statements)

References 7 publications

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“…Alendronate 100 mM significantly induced apoptosis in primary cultures of alveolar macrophages and in established MH-S cells, though this concentration is much higher than plasma concentrations (o0.25-0.34 mM) in humans administered therapeutic doses of 5-10 mg per day or 70 mg per week 31 . However, the alendronate dose administered to mice via aerosol inhalation was 3.25 mg, which was comparable to that used orally for the treatment of human bone diseases (B5 mg per 50 kg).…”

Section: Discussionmentioning

confidence: 96%

Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages

et al. 2015

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Alveolar macrophages play a crucial role in the pathogenesis of emphysema, for which there is currently no effective treatment. Bisphosphonates are widely used to treat osteoclastmediated bone diseases. Here we show that delivery of the nitrogen-containing bisphosphonate alendronate via aerosol inhalation ameliorates elastase-induced emphysema in mice. Inhaled, but not orally ingested, alendronate inhibits airspace enlargement after elastase instillation, and induces apoptosis of macrophages in bronchoalveolar fluid via caspase-3-and mevalonate-dependent pathways. Cytometric analysis indicates that the F4/80 þ CD11b high CD11c mild population characterizing inflammatory macrophages, and the F4/80 þ CD11b mild CD11c high population defining resident alveolar macrophages take up substantial amounts of the bisphosphonate imaging agent OsteoSense680 after aerosol inhalation. We further show that alendronate inhibits macrophage migratory and phagocytotic activities and blunts the inflammatory response of alveolar macrophages by inhibiting nuclear factor-kB signalling. Given that the alendronate inhalation effectively induces apoptosis in both recruited and resident alveolar macrophages, we suggest this strategy may have therapeutic potential for the treatment of emphysema.

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Section: Discussionmentioning

confidence: 96%

Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages

et al. 2015

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“…Oral ALN has poor bioavailability (0.7% to 1%) (20,21) and inconvenient dosing requirements (participants must dose 30 to 60 minutes before breakfast with just water and delay first food or drink of the day and remain upright for at least 30 minutes after drug ingestion). Although not evident in controlled trials of oral bisphosphonates (including this trial), gastrointestinal side effects may occur, including reflux, esophagitis, gastritis, and ulcers.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of a once-yearly i.v. Infusion of zoledronic acid 5 mg versus a once-weekly 70-mg oral alendronate in the treatment of male osteoporosis: A randomized, multicenter, double-blind, active-controlled study

Orwoll

Miller

Adachi

et al. 2010

Journal of Bone and Mineral Research

162

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Zoledronic acid (ZOL) has shown beneficial effects on bone turnover and bone mineral density (BMD) in postmenopausal osteoporosis. This study compared the efficacy and safety of a once-yearly i.v. infusion of ZOL with weekly oral alendronate (ALN) in men with osteoporosis. In this multicenter, double-blind, active-controlled, parallel-group study, participants (n ¼ 302) were randomized to receive either once-yearly ZOL 5 mg i.v. or weekly oral ALN 70 mg for 24 months. Changes in BMD and bone marker levels were assessed. ZOL increased BMD at the lumbar spine, total hip, femoral neck, and trochanter and was not inferior to ALN at 24 months [least squares mean estimates of the percentage increases in lumbar spine BMD of 6.1% and 6.2%; difference approximately 0.13; 95% confidence interval (CI) 1.12-0.85 in the ZOL and ALN groups, respectively]. At month 12, the median change from baseline of markers for bone resorption [serum b-C-terminal telopeptide of type I collagen (b-CTx) and urine N-terminal telopeptide of type I collagen (NTx)] and formation [serum N-terminal propeptide of type I collagen (P1NP) and serum bone-specific alkaline phosphatase (BSAP)] were comparable between ZOL and ALN groups. Most men preferred i.v. ZOL over oral ALN. The incidence of adverse events and serious adverse events was similar in the treatment groups. It is concluded that a once-yearly i.v. infusion of ZOL 5 mg increased bone density and decreased bone turnover markers similarly to once-weekly oral ALN 70 mg in men with low bone density. ß

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“…Generic versions of alendronate have been reported to be bioequivalent to branded alendronate (Rhim et al 2009 ; Yun et al 2006 ; Lainesse et al 2004 ). The development of a brand name formulation requires the demonstration of its pharmacokinetics, efficacy and tolerability in both healthy subjects and in the target patient population.…”

Section: Resultsmentioning

confidence: 99%

A critical review of brand and generic alendronate for the treatment of osteoporosis

et al. 2013

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ObjectiveCompare in vitro and in vivo characteristics and clinical outcomes of brand and generic alendronate.Research design and methods: Relevant search terms were input into Medline ("alendronate" AND "generic" up to August 5, 2013) and any abstracts deemed possibly relevant selected for full paper review and abstraction.ResultsMulticentre, randomized, placebo-controlled Phase III clinical trials of substantial size and duration have established the anti-fracture efficacy and safety of brand amino-bisphosphonates. For regulatory approval, generic versions of brand drugs need to demonstrate bioequivalence in young, healthy volunteers and have similar dissolution times. While the potency and amount of active drug within generic formulations must be identical to the brand, differences are permitted in the excipients. Significant differences in tablet disintegration time among different versions of generic and brand alendronate have been reported. Rapidly disintegrating alendronate pills may increase oesophageal bioadhesion and adverse event risk. Oesophageal-bound alendronate or slow disintegrating alendronate tablets may be made inert and ineffective by subsequently ingested food or drink. Investigations have reported a lower persistence to therapy with generic brands of alendronate as compared to brand bisphosphonates and patients switched from brand to generic alendronate have increased adverse event rates and losses in bone mineral density.ConclusionNumerous differences exist between brand and generic alendronate including: disintegration time, bioadhesion to the oesophagus, patient persistence to therapy, adverse event incidence, and maintenance of bone mineral density. Generic forms of alendronate warrant closer clinical study before they are ascribed the clinical effectiveness and tolerability of brand alendronate.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-2-550) contains supplementary material, which is available to authorized users.

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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

Cited by 16 publications

References 7 publications

Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages

Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages

Efficacy and safety of a once-yearly i.v. Infusion of zoledronic acid 5 mg versus a once-weekly 70-mg oral alendronate in the treatment of male osteoporosis: A randomized, multicenter, double-blind, active-controlled study

A critical review of brand and generic alendronate for the treatment of osteoporosis

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