Effect of obesity on pharmacokinetics and biologic effect of interferon-α in hepatitis C

被引:45
作者
Lam N.P. [1 ]
Pitrak D. [1 ]
Speralakis R. [1 ]
Lau A.H. [1 ]
Wiley T.E. [1 ]
Layden T.J. [1 ]
机构
[1] Department of Pharmacy Practice, College of Pharmacy, Chicago, IL 60612
关键词
2'; 5'-oligoadenylate synthetase; chronic hepatitis C; histologic activity index; interferon-α; obesity;
D O I
10.1023/A:1018865928308
中图分类号
学科分类号
摘要
To examine potential adverse effects of obesity in reducing the response to interferon-α (IFN-α) in chronic hepatitis C (HCV), IFN-α and HCV RNA levels in serum and the 2',5'-oligoadenylate synthetase (2-5 OAS) levels in peripheral blood mononuclear cells (PBMC) were compared between six obese and five nonobese patients before and after a single, 10 mIU dose of IFN-α(2b). There were no differences in the mean histologic activity index between the two groups. The maximal IFN concentration and the area under the serum IFN concentration-time curve were higher in nonobese patients. These two parameters were inversely correlated with body weight and body surface area. No differences were found in the mean reduction in HCV RNA levels between the two groups following IFN-α. The maximal 2-5 OAS level after treatment divided by the pretreatment 2-5 OAS level (2-5 OAS response ratio) was greater in the nonobese patients, suggesting stronger biologic response upon exposure to exogenous IFN-α in nonobese patients.
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页码:178 / 185
页数:7
相关论文
共 41 条
[1]  
Davis G.L., Balart L.A., Schiff E.R., Lindsay K., Bodenheimer Jr. H.C., Perrillo R.P., Carey W., Jacobson I.M., Payne J., Dienstag J.L., Van Thiel D.H., Tamburro C.F., Lefkowitch J., Albrecht J., Meschievitz C., Ortego T.J., Gibas A., Treatment of chronic hepatitis C with recombinant interferon alfa: A multicenter, randomized, controlled study, N Engl J Med, 321, pp. 1501-1506, (1989)
[2]  
Di Bisceglie A.M., Martin P., Kassianides C., Lisker-Melman M., Murray L., Waggoner J., Goodman Z., Banks S.M., Hoofnagle J.H., Recombinant interferon alfa therapy for chronic hepatitis C
[3]  
a randomized double-blind placebo-controlled trial, N Engl J Med, 321, pp. 1506-1510, (1989)
[4]  
Lau J.Y.N., David G.L., Kniffen J., Qian K.P., Urdea M.S., Chan C.S., Mizokami M., Neuwald P.D., Wilber J.C., Significance of serum hepatitis C virus RNA levels in chronic hepatitis, Lancet, 341, pp. 1501-1504, (1993)
[5]  
Hagiwara H., Hayashi N., Mita E., Takehara J., Kasahara A., Hideyuki F., Kamada T., Quantitative analysis of hepatitis C virus RNA in serum during interferon alfa therapy, Gastroenterology, 104, pp. 877-893, (1993)
[6]  
Shindo M., DiBisceglie A.M., Hoofnagle J.H., Long term follow up of patients with chronic hepatitis C treated with alpha-interferon, Hepatology, 15, pp. 1013-1016, (1992)
[7]  
Okada S., Akahane Y., Suzuki H., Okamoto H., Mishiro S., The degree of variability in the amino terminal regions of the E2/NS1 protein of hepatitis C virus correlates with responsiveness to interferon therapy in viremic patients, Hepatology, 16, pp. 619-624, (1992)
[8]  
Tsubota A., Chayama K., Ikeda K., Yasuji A., Koida I., Saitoh S., Hashimoto M., Iwasaki S., Kobayashi M., Hiromitsu K., Factors predictive of response to interferon-α therapy in hepatitis C virus infection, Hepatology, 19, pp. 1088-1094, (1994)
[9]  
Yoshioka K., Kakumu S., Wakita T., Ishikama T., Itoh Y., Takayanagi M., Higashi Y., Shibata M., Morishima T., Detection of hepatitis C virus by polymerase chain reaction and response to interferon-α therapy: Relationship to genotypes of hepatitis C virus, Hepatology, 16, pp. 293-299, (1992)
[10]  
Perez R., Pravia R., Linares A., Rodriguez M., Lombrana J.L.S., Suarez A., Riestra S., Navascues C.A., Rodrigo L., Response related factors in recombinant interferon alfa-2b treatment of chronic hepatitis C, Gut, 34, SUPPL., (1993)