Pharmacokinetic and therapeutic efficacy of intrapulmonary administration of zoledronate for the prevention of bone destruction in rheumatoid arthritis
| Autor: | Tomohiro Hasei, Takunori Mozume, Tetsushi Watanabe, Toshiyasu Sakane, Hidemasa Katsumi, Shin-ichiro Yanagi, Akira Yamamoto |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_treatment 030232 urology & nephrology Pharmaceutical Science Absorption (skin) Pharmacology Zoledronic Acid 030226 pharmacology & pharmacy Bone and Bones Arthritis Rheumatoid Mice 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems 0302 clinical medicine Therapeutic index Pharmacokinetics medicine Animals Rats Wistar Lung Creatinine Bone Density Conservation Agents Diphosphonates medicine.diagnostic_test business.industry Imidazoles Bisphosphonate medicine.disease Arthritis Experimental Rats Bioavailability Disease Models Animal Bronchoalveolar lavage chemistry Mice Inbred DBA Rheumatoid arthritis Collagen business Bronchoalveolar Lavage Fluid |
| Zdroj: | Journal of Drug Targeting. 24:530-536 |
| ISSN: | 1029-2330 1061-186X |
| DOI: | 10.3109/1061186x.2015.1101768 |
| Popis: | Zoledronate, a third-generation nitrogen-containing bisphosphonate, is a new therapeutic agent for the prevention of joint destruction in rheumatoid arthritis (RA). Due to the poor oral absorption of zoledronate, the intravenous route has been the preferred method of administration. To evaluate whether the lung is a promising alternative route of zoledronate administration for the prevention of joint destruction in RA, we examined the pharmacokinetics, safety and therapeutic potential of zoledronate after intrapulmonary administration. The bioavailability of zoledronate was 55% after intrapulmonary administration in rats. In a collagen-induced RA mouse model, an intrapulmonary administration of zoledronate given 7 d before the 2nd collagen immunization effectively suppressed bone loss and joint destruction to a level similar to that achieved with intravenous injection at 21 d after the 2nd collagen immunization. Zoledronate only slightly affected lactate dehydrogenase activity in bronchoalveolar lavage fluid 4 h after intrapulmonary administration of the therapeutic dose in rats. Moreover, zoledronate only slightly changed the plasma level of creatinine after intrapulmonary administration while creatinine significantly increased after intravenous injection of zoledronate in mice. These results indicate that the lung is a promising alternative route of zoledronate administration for the treatment and prevention of joint destruction in RA. |
| Databáze: | OpenAIRE |
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