Abstract
Both (+)-cyclaradine-5'-methoxyacetate (CM) and (+)-cyclaradine-5'-ethoxypropionate (CE) were converted to (+)-cyclaradine (C) in squirrel monkey and human sera at 37 degrees C. CE was more stable than CM. After oral administration (20 mg base equivalent per kg) of either CM or CE, no unchanged esters were observed in serum of squirrel monkeys, rabbits, or rats. Instead, C was detected, indicating conversions of CM and CE to C in vivo. In squirrel monkeys, the areas under the curve (AUCs) of C obtained from oral dosing with CM were 61% higher than those obtained from dosing with C, indicating that CM may be a good prodrug for C. In squirrel monkeys, rabbits, and rats, CE resulted in a 20 to 90% higher AUC of C than did CM, indicating that CE was better absorbed than CM.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Lim J. M., Lin C. C. Column-switching high-performance liquid chromatographic method for determination of a new antiviral agent, cyclaradine, in serum. Antimicrob Agents Chemother. 1986 Jun;29(6):977–979. doi: 10.1128/aac.29.6.977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz J., Ostrander M., Butkiewicz N. J., Lieberman M., Lin C., Lim J., Miller G. H. Activity of (+)-cyclaradine (Sch 31172) against herpes simplex virus in vitro and in vivo. Antimicrob Agents Chemother. 1987 Jan;31(1):21–26. doi: 10.1128/aac.31.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shannon W. M., Westbrook L., Arnett G., Daluge S., Lee H., Vince R. Comparison of the efficacy of vidarabine, its carbocyclic analog (cyclaradine), and cyclaradine-5'-methoxyacetate in the treatment of herpes simplex virus type 1 encephalitis in mice. Antimicrob Agents Chemother. 1983 Oct;24(4):538–543. doi: 10.1128/aac.24.4.538. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vince R., Daluge S. Carbocyclic arabinosyladenine, an adenosine deaminase resistant antiviral agent. J Med Chem. 1977 Apr;20(4):612–613. doi: 10.1021/jm00214a040. [DOI] [PubMed] [Google Scholar]
- Vince R., Daluge S., Lee H., Shannon W. M., Arnett G., Schafer T. W., Nagabhushan T. L., Reichert P., Tsai H. Carbocyclic arabinofuranosyladenine (cyclaradine): efficacy against genital herpes in guinea pigs. Science. 1983 Sep 30;221(4618):1405–1406. doi: 10.1126/science.6684328. [DOI] [PubMed] [Google Scholar]