No abstract

Ribavirin, 1-,-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole; Viratek, Inc., Covina, Calif.), has a broad spectrum of antiviral activity. However, the study of the absorption, metabolism, and excretion of this compoupd has been limited by the lack of an appropriate assay for ribavirin and its metabolites. Since ribavirin has definite potential for therapeutic use, we developed a radioimmunoassay to measure ribavirin levels in clinical specimens. To prepare an effective immunogen, ribavirin was monosuccinylated and coupled to ovalbumin. The competitive binding radioimmunoassay, in which tritium-labeled ribavirin and rabbit antiribavirin serum were used, was quantitative for ribavirin at concentrations of 1 pmol/100 ,ul in urine or plasma samples. The rabbit antibody cross-reacted with the major metabolite of ribavirin, 1,2,4-triazole-3-carboxamide, at a low level (2 to 5%) which did not interfere with ribavirin binding until concentrations of 1,2,4-triazole-3-carboxamide 10-to 100-fold higher than ribavirin were present in mock samples, a condition not present in biological specimens. We used the ribavirin radioimmunoassay to determine the ribavirin concentration in mouse plasma after intraperitoneal administration, in the sera of adults fromn Sierra Leone after oral or intravenous administration for treatment of suspected Lassa fever, and in the sera of children in the United States after smallparticle aerosol administration. Our experience with the radioimmunoassay indicates that it is sensitive, accurate, and reproducible. The assay will permit studies leading to a better understanding of the pharmacology and pharmacokinetics of this potentially useful antiviral drug.The synthetic nucleoside-like compound ribavirin (1-,-D-ribofuranosyl-1,2,4-triazole-3-carboxamide; Virazole; Virjtek, Inc., Covina, Cal-

No abstract

No abstract

The magnitude of the Balb/c mouse IgA anti-alpha (1 leads to 3) dextran B1355 (anti-dex) response in vivo was recently found to be markedly T-cell-dependent and age-dependent. This report demonstrates that the in vitro IgA anti-dex response by mesenteric lymph nodes (MLN) is highly age-dependent and that there is an age-dependent increase of the background IgA anti-dex plaque-forming cell (PFC) response occurring in the absence of added antigen which correlates significantly with the magnitude of the antigen-stimulated response. In aging mice both background and antigen-stimulated IgA anti-dex responses appeared to be significantly higher in MLN than in spleen cultures. Moreover, it is shown that there is a striking increase with age of natural antibody in the serum of normal Balb/c to alpha (1 leads to 3) glucan determinants, particularly IgA and lesser amounts of IgM and IgG3.