This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hsu, A.
Right arrow Articles by Sun, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hsu, A.
Right arrow Articles by Sun, E.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 1998, p. 2784-2791, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Pharmacokinetic Interaction between Ritonavir and Indinavir in Healthy Volunteers

Ann Hsu,* G. Richard Granneman, Guoliang Cao, Lori Carothers, Anthony Japour, Tawakol El-Shourbagy, Suzana Dennis, Jeanne Berg, Keith Erdman, John M. Leonard, and Eugene Sun

Abbott Laboratories, Abbott Park, Illinois

Received 5 March 1998/Returned for modification 25 May 1998/Accepted 11 August 1998

The pharmacokinetic interaction between indinavir and ritonavir was evaluated in five groups of healthy adult volunteers to explore the potential for twice-daily (b.i.d.) dosing of this combination. All subjects received 800 mg of indinavir every 8 h (q8h) on day 2. In addition, subjects in group I received one dose of 800 mg of indinavir on day 1 and 800 mg of indinavir q8h on day 17. Subjects in Groups II and IV each received one dose of 600 mg of indinavir on days 1 and 17, and subjects in groups III and V each received one dose of 400 mg of indinavir on days 1 and 17. During days 3 to 17, ritonavir placebo or ritonavir at 200, 300, 300, or 400 mg q12h was given to groups I, II, III, IV, and V, respectively. Ritonavir at steady state probably inhibited the cytochrome P-450 3A metabolism of indinavir and substantially increased plasma indinavir concentrations, with the area under the plasma concentration-time curve (AUC) increasing up to 475% and the peak concentration in serum (Cmax) increasing up to 110%. The Cmax/trough concentration ratio decreased from 50 in standard q8h regimens to less than 14 when indinavir was administered with ritonavir. For a constant indinavir dose, an increase in the ritonavir dose yielded similar indinavir AUCs, Cmaxs, and concentrations at 12 h (C12s). For a constant ritonavir dose, an increase in the indinavir dose resulted in approximately proportional increases in the indinavir AUC, less than proportional increases in Cmax, and slightly more than proportional increases in C12. Ritonavir reduced between-subject variability in the indinavir AUC and trough concentrations and did not affect indinavir renal clearance. With the altered pharmacokinetic profile, indinavir likely could be given as a b.i.d. combination regimen with ritonavir. This could potentially improve patient compliance and thereby reduce treatment failures.

* Corresponding author. Mailing address: Abbott Laboratories, D-4PK, AP13A, 100 Abbott Park Rd., Abbott Park, IL 60064-3500. Phone: (708) 937-2961. Fax: (708) 938-5193. E-mail: Ann.Hsu{at}Abbott.com.

Antimicrobial Agents and Chemotherapy, November 1998, p. 2784-2791, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Shou, M., Hayashi, M., Pan, Y., Xu, Y., Morrissey, K., Xu, L., Skiles, G. L. (2008). Modeling, Prediction, and in Vitro in Vivo Correlation of CYP3A4 Induction. Drug Metab. Dispos. 36: 2355-2370 [Abstract] [Full Text]  
  • Kharasch, E. D., Mitchell, D., Coles, R., Blanco, R. (2008). Rapid Clinical Induction of Hepatic Cytochrome P4502B6 Activity by Ritonavir. Antimicrob. Agents Chemother. 52: 1663-1669 [Abstract] [Full Text]  
  • Cuevas Gonzalez, M. J., Valin, L. O., Perez-Simon, M. d. R., Mostaza Fernandez, J. L., Alcoba Leza, M., Sanchez, V. M., the HAART Adherence Working Group of the Province, (2007). A Prospective Study of Adherence and Virologic Failure in HIV-Infected Patients: Role of a Single Determination of Plasma Levels of Antiretroviral Medications. J Int Assoc Physicians AIDS Care (Chic Ill) 6: 245-250 [Abstract]  
  • Ferguson, N.M, Donnelly, C.A, Hooper, J, Ghani, A.C, Fraser, C, Bartley, L.M, Rode, R.A, Vernazza, P, Lapins, D, Mayer, S.L, Anderson, R.M (2005). Adherence to antiretroviral therapy and its impact on clinical outcome in HIV-infected patients. J R Soc Interface 2: 349-363 [Abstract] [Full Text]  
  • la Porte, C., Verweij-van Wissen, C., van Ewijk, N., Aarnoutse, R., Koopmans, P., Reiss, P., Stek, M. Jr, Hekster, Y., Burger, D. (2005). Pharmacokinetic Interaction Study of Indinavir/Ritonavir and the Enteric-Coated Capsule Formulation of Didanosine in Healthy Volunteers. J Clin Pharmacol 45: 211-218 [Abstract] [Full Text]  
  • Rhame, F. S., Rawlins, S. L., Petruschke, R. A., Erb, T. A., Winchell, G. A., Wilson, H. M., Edelman, J. M., Abramson, M. A. (2004). Pharmacokinetics of Indinavir and Ritonavir Administered at 667 and 100 Milligrams, Respectively, Every 12 Hours Compared with Indinavir Administered at 800 Milligrams Every 8 Hours in Human Immunodeficiency Virus-Infected Patients. Antimicrob. Agents Chemother. 48: 4200-4208 [Abstract] [Full Text]  
  • Ruxrungtham, K., Boyd, M., Bellibas, S. E., Zhang, X., Dorr, A., Kolis, S., Kinchelow, T., Buss, N., Patel, I. H. (2004). Lack of Interaction between Enfuvirtide and Ritonavir or Ritonavir-Boosted Saquinavir in HIV-1-Infected Patients. J Clin Pharmacol 44: 793-803 [Abstract] [Full Text]  
  • Bergshoeff, A. S., Fraaij, P. L. A., van Rossum, A. M. C., Verweel, G., Wynne, L. H., Winchell, G. A., Leavitt, R. Y., Nguyen, B.-Y. T., de Groot, R., Burger, D. M. (2004). Pharmacokinetics of Indinavir Combined with Low-Dose Ritonavir in Human Immunodeficiency Virus Type 1-Infected Children. Antimicrob. Agents Chemother. 48: 1904-1907 [Abstract] [Full Text]  
  • Sheehan, N. L, Kelly, D. V, Tseng, A. L, van Heeswijk, R. P., Beique, L. C, Hughes, C. A (2003). Evaluation of HIV Drug Interaction Web Sites. The Annals of Pharmacotherapy 37: 1577-1586 [Abstract] [Full Text]  
  • Haas, D. W., Johnson, B., Nicotera, J., Bailey, V. L., Harris, V. L., Bowles, F. B., Raffanti, S., Schranz, J., Finn, T. S., Saah, A. J., Stone, J. (2003). Effects of Ritonavir on Indinavir Pharmacokinetics in Cerebrospinal Fluid and Plasma. Antimicrob. Agents Chemother. 47: 2131-2137 [Abstract] [Full Text]  
  • Burger, D., Boyd, M., Duncombe, C., Felderhof, M., Mahanontharit, A., Ruxrungtham, K., Ubolyam, S., Stek, M., Cooper, D., Lange, J., Phanupak, P., Reiss, P. (2003). Pharmacokinetics and pharmacodynamics of indinavir with or without low-dose ritonavir in HIV-infected Thai patients. J Antimicrob Chemother 51: 1231-1238 [Abstract] [Full Text]  
  • Shulman, N., Zolopa, A., Havlir, D., Hsu, A., Renz, C., Boller, S., Jiang, P., Rode, R., Gallant, J., Race, E., Kempf, D. J., Sun, E. (2002). Virtual Inhibitory Quotient Predicts Response to Ritonavir Boosting of Indinavir-Based Therapy in Human Immunodeficiency Virus-Infected Patients with Ongoing Viremia. Antimicrob. Agents Chemother. 46: 3907-3916 [Abstract] [Full Text]  
  • Dieleman, J. P., Sturkenboom, M. C. J. M., Jambroes, M., Gyssens, I. C., Weverling, G.-J., ten Veen, J. H., Schrey, G., Reiss, P., Stricker, B. H. Ch., for the ATHENA Study Group, (2002). Risk Factors for Urological Symptoms in a Cohort of Users of the HIV Protease Inhibitor Indinavir Sulfate: The ATHENA Cohort. Arch Intern Med 162: 1493-1501 [Abstract] [Full Text]  
  • Walmsley, S., Bernstein, B., King, M., Arribas, J., Beall, G., Ruane, P., Johnson, M., Johnson, D., Lalonde, R., Japour, A., Brun, S., Sun, E., the M98-863 Study Team, (2002). Lopinavir-Ritonavir versus Nelfinavir for the Initial Treatment of HIV Infection. NEJM 346: 2039-2046 [Abstract] [Full Text]  
  • Estaquier, J., Lelievre, J.-D., Petit, F., Brunner, T., Moutouh-de Parseval, L., Richman, D. D., Ameisen, J. C., Corbeil, J. (2002). Effects of Antiretroviral Drugs on Human Immunodeficiency Virus Type 1-Induced CD4+ T-Cell Death. J. Virol. 76: 5966-5973 [Abstract] [Full Text]  
  • Sale, M., Sadler, B. M., Stein, D. S. (2002). Pharmacokinetic Modeling and Simulations of Interaction of Amprenavir and Ritonavir. Antimicrob. Agents Chemother. 46: 746-754 [Abstract] [Full Text]  
  • Piccinini, G., Foli, A., Comolli, G., Lisziewicz, J., Lori, F. (2002). Complementary Antiviral Efficacy of Hydroxyurea and Protease Inhibitors in Human Immunodeficiency Virus-Infected Dendritic Cells and Lymphocytes. J. Virol. 76: 2274-2278 [Abstract] [Full Text]  
  • Saah, A. J., Winchell, G. A., Nessly, M. L., Seniuk, M. A., Rhodes, R. R., Deutsch, P. J. (2001). Pharmacokinetic Profile and Tolerability of Indinavir-Ritonavir Combinations in Healthy Volunteers. Antimicrob. Agents Chemother. 45: 2710-2715 [Abstract] [Full Text]  
  • Piscitelli, S. C., Gallicano, K. D. (2001). Interactions among Drugs for HIV and Opportunistic Infections. NEJM 344: 984-996 [Full Text]  
  • Burger, D. M., van Rossum, A. M. C., Hugen, P. W. H., Suur, M. H., Hartwig, N. G., Geelen, S. P. M., Scherpbier, H. J., Hoetelmans, R. M. W., Vulto, A. G., de Groot, R. (2001). Pharmacokinetics of the Protease Inhibitor Indinavir in Human Immunodeficiency Virus Type 1-Infected Children. Antimicrob. Agents Chemother. 45: 701-705 [Abstract] [Full Text]  
  • Brophy, D. F., Israel, D. S., Pastor, A., Gillotin, C., Chittick, G. E., Symonds, W. T., Lou, Y., Sadler, B. M., Polk, R. E. (2000). Pharmacokinetic Interaction between Amprenavir and Clarithromycin in Healthy Male Volunteers. Antimicrob. Agents Chemother. 44: 978-984 [Abstract] [Full Text]  
  • Carpenter, C. C. J., Cooper, D. A., Fischl, M. A., Gatell, J. M., Gazzard, B. G., Hammer, S. M., Hirsch, M. S., Jacobsen, D. M., Katzenstein, D. A., Montaner, J. S. G., Richman, D. D., Saag, M. S., Schechter, M., Schooley, R. T., Thompson, M. A., Vella, S., Yeni, P. G., Volberding, P. A. (2000). Antiretroviral Therapy in Adults: Updated Recommendations of the International AIDS Society-USA Panel. JAMA 283: 381-390 [Abstract] [Full Text]  
  • Kumar, G. N., Dykstra, J., Roberts, E. M., Jayanti, V. K., Hickman, D., Uchic, J., Yao, Y., Surber, B., Thomas, S., Granneman, G. R. (1999). Potent Inhibition of the Cytochrome P-450 3A-Mediated Human Liver Microsomal Metabolism of a Novel HIV Protease Inhibitor by Ritonavir: A Positive Drug-Drug Interaction. Drug Metab. Dispos. 27: 902-908 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»