+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Pharmacokinetics and disposition of CS-8958, a long-acting prodrug of the novel neuraminidase inhibitor laninamivir in rats

, : Pharmacokinetics and disposition of CS-8958, a long-acting prodrug of the novel neuraminidase inhibitor laninamivir in rats. Xenobiotica; the Fate of Foreign Compounds in Biological Systems 40(3): 207-216

CS-8958, a prodrug of laninamivir (R-125489), is currently under development as an inhaled anti-influenza drug. In this study, the pharmacokinetics and disposition of CS-8958 were characterized in rats. After intratracheal administration of 14C-CS-8958, radioactivity was retained over long periods in the target tissues (trachea and lung) as its active metabolite R-125489 - 19.12% of the dose was retained in the lung at 24 h. After intratracheal administration of CS-8958, plasma R-125489 concentration was slowly eliminated, and its half-life (14.1 h) was considerably longer than that after intravenous administration of R-125489. The radioactivity of intratracheally administered 14C-CS-8958 was mainly excreted into the urine (67.5% of dose), and this excretion lasted over long periods. R-125489 accounted for most of the urinary radioactivity recovered after 24 h. These results demonstrated that CS-8958 administered intratracheally to rats was converted/hydrolysed to R-125489 in the target tissues, and that the R-125489 was slowly excreted into the urine via an absorption rate-limiting process. Such distinctive pharmacokinetics attributed to the slow release of R-125489 suggests the potential for a long-acting anti-influenza drug.


PMID: 20146556

DOI: 10.3109/00498250903447691

Other references

Mowitz, D., 1988: Wrapping up hay harvest in a whole new way. Successful farming 86(8): 42-43

Tovbin, D.; Sherman, R.A., 2015: Correcting Acidosis during Hemodialysis: Current Limitations and a Potential Solution. The deleterious catabolic and pro-inflammatory effects of acidosis in hemodialysis (HD) patients and the importance of its correction for limiting mineral bone disease (MBD) are well known. Although oral base therapy could be a solution for correc...

Drake, C.T.; Lewis, F.J., 1961: The plasma volume expanding effect of low molecular weight dextran in the hypothermic dog. Surgical Forum 12: 182-184

Falick, J., 1975: Designing cheap buildings is expensive. Hospitals 49(3): 125-7, 129-30

Watanabe, H.; Uruma, T.; Tazaki, G.; Kikuchi, R.; Tsuji, T.; Itoh, M., 2015: Clinical factors associated with negative urinary antigen tests implemented for the diagnosis of community-acquired pneumococcal pneumonia in adult patients. This study investigated clinical factors associated with negative urinary antigen tests (UAT) implemented for the diagnosis of pneumococcal community-acquired pneumonia (CAP) in adult patients. We reviewed the medical records of 755 adult patients...

Wiener, R.Constance., 2015: Dental Fear and Delayed Dental Care in Appalachia-West Virginia. The people of Appalachia-West Virginia are culturally unique and are known to have oral health disparities. The purpose of this study was to evaluate dental fear in relation to delayed dental care as a factor influencing oral health behaviors with...

Tompsett, S.L.; Oastler, E.G., 1948: The neutral steroids of human urine; the significance of the various steroid fractions excreted in urine. Glasgow Medical Journal 29(5): 133-156

Londry, F.A.; Alfred, R.L.; March, R.E., 1993: Computer simulation of single-ion trajectories in paul-type ion traps. The computer simulation of single-ion trajectories using a number of computer programs is described together with associated theory. The programs permit calculation of ion trajectories while the ion is subjected to collisions with buffer gas of va...

Zilliacus, J.; Wright, A.P.; Norinder, U.; Gustafsson, J.A.; Carlstedt-Duke, J., 1992: Determinants for DNA-binding site recognition by the glucocorticoid receptor. The glucocorticoid receptor binds with high specificity to glucocorticoid response elements, discriminating them from other closely related binding sites. Three amino acids in the recognition alpha-helix of the DNA-binding domain of the receptor a...

Despons, J., 1968: Vasomotor facial algia. Revue de Laryngologie - Otologie - Rhinologie 89(1): 91-95