{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:18:02Z","timestamp":1777418282835,"version":"3.51.4"},"reference-count":23,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2003,4,1]],"date-time":"2003-04-01T00:00:00Z","timestamp":1049155200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2003,4]]},"abstract":"\n OBJECTIVE:<\/jats:title>\n To describe a case of successful protease inhibitor\u2013based highly active antiretroviral therapy (HAART) concomitant with rifampin.<\/jats:p>\n <\/jats:sec>\n \n CASE SUMMARY:<\/jats:title>\n \n In a 7-month-old male infant with tuberculosis and HIV-1 infection, tuberculosis therapy including rifampin and HAART containing the protease inhibitor nelfinavir 40 mg\/kg every 8 hours was started. Intensive steady-state pharmacokinetic sampling from baseline to 8 hours revealed very low plasma concentrations of nelfinavir: area under the plasma concentration\u2013time curve (AUC\n 0\u201324<\/jats:sub>\n ) <10% of adult population values for 750 mg every 8 hours and nonquantifiable concentrations of nelfinavir's principal metabolite (M8). Nelfinavir 40 mg\/kg every 8 hours was then substituted with nelfinavir 30 mg\/kg twice daily plus ritonavir 400 mg\/m\n 2<\/jats:sup>\n twice daily. Intensive steady-state (0\u201312 h) pharmacokinetic sampling was repeated. Nelfinavir concentrations had improved, but remained low when compared with adult population values of 1250 mg every 12 hours: AUC\n 0\u201324<\/jats:sub>\n 21.9 versus 47.6 mg\/L\u2022h (46%) and 12-hour trough level (C\n 12<\/jats:sub>\n ) 0.25 versus 0.85 mg\/L (29%). However, concentrations of M8 considerably exceeded population values: AUC\n 0\u201324<\/jats:sub>\n 57.5 versus 13.6 mg\/L\u2022h (443%) and C\n 12<\/jats:sub>\n 1.35 versus 0.28 mg\/L (482%). Since M8 concentrations were highly elevated, pharmacokinetic parameters for (nelfinavir + M8) were used rather than those for nelfinavir alone. Thus, AUC\n 0\u201324<\/jats:sub>\n (nelfinavir + M8) and C\n 12<\/jats:sub>\n (nelfinavir + M8) comprised 130% and 142%, respectively of the adult population values. This, in addition to good clinical response and tolerability, favored continuation of the regimen.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n In an infant, nelfinavir-containing HAART was successfully used with rifampin after the addition of ritonavir. Ritonavir resolved the pharmacokinetic interaction between rifampin and nelfinavir by boosting nelfinavir and, especially, M8 concentrations. More research is needed to confirm these results.<\/jats:p>\n <\/jats:sec>","DOI":"10.1345\/aph.1c335","type":"journal-article","created":{"date-parts":[[2003,3,27]],"date-time":"2003-03-27T13:04:20Z","timestamp":1048770260000},"page":"521-525","source":"Crossref","is-referenced-by-count":8,"title":["Ritonavir-Enhanced Pharmacokinetics of Nelfinavir\/M8 during Rifampin Use"],"prefix":"10.1177","volume":"37","author":[{"given":"Alina S","family":"Bergshoeff","sequence":"first","affiliation":[{"name":"Alina S Bergshoeff PharmD, Research Pharmacologist, Department of Clinical Pharmacy, University Medical Center, Nijmegen, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom FW","family":"Wolfs","sequence":"additional","affiliation":[{"name":"Tom FW Wolfs MD PhD, Pediatrician, University Medical Center\/Wilhelmina Children's Hospital, Department of Infectious Diseases, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sibyl PM","family":"Geelen","sequence":"additional","affiliation":[{"name":"Sibyl PM Geelen MD PhD, Pediatrician, University Medical Center\/Wilhelmina Children's Hospital, Department of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M","family":"Burger","sequence":"additional","affiliation":[{"name":"David M Burger PharmD PhD, Assistant Professor of Clinical Pharmacology\/Hospital Pharmacist, Department of Clinical Pharmacy, University Medical Center, Nijmegen"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2003,4,1]]},"reference":[{"key":"bibr1-aph.1C335","volume-title":"Pediatric pharmacology: therapeutic principles in practice","author":"Yaffe SJ","year":"1992","edition":"2"},{"key":"bibr2-aph.1C335","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200103293441307"},{"key":"bibr3-aph.1C335","volume-title":"Product information. Viracept (rifampin)","year":"2001"},{"key":"bibr4-aph.1C335","first-page":"185","volume":"49","year":"2000","journal-title":"Morb Mortal Wkly Rep"},{"key":"bibr5-aph.1C335","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.4.1086-1093.2001"},{"key":"bibr6-aph.1C335","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(99)00079-1"},{"key":"bibr7-aph.1C335","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200105250-00007"},{"key":"bibr8-aph.1C335","unstructured":"8 Gibaldi M. Biopharmaceutics and clinical pharmacokinetics. 4th ed. Philadelphia: Lea & Febiger, 1999: 14\u201323."},{"key":"bibr9-aph.1C335","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200059030-00014"},{"key":"bibr10-aph.1C335","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199835040-00002"},{"key":"bibr11-aph.1C335","doi-asserted-by":"publisher","DOI":"10.1097\/00126334-200202011-00003"},{"key":"bibr12-aph.1C335","unstructured":"12 Lillibridge JH, Lee CA, Pithavala YK, Daniels RG, Samuel TM, Wu EY, et al. The role of polymorphic CYP 2C19 in the metabolism of nelfinavir mesylate (abstract 3035). Presented at: 12th Annual Meeting, American Association of Pharmaceutical Scientists, San Francisco, November 15\u201319, 1998."},{"key":"bibr13-aph.1C335","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-200108000-00006"},{"key":"bibr14-aph.1C335","unstructured":"14 Hsyu PH, Capparelli EV, Amantea M, Petersen A, Kerr BM. Population pharmacokinetics (PK) of TID nelfinavir (NFV) and correlation to efficacy in pediatric patients (abstract 348).opulation pharmacokinetics (PK) of TID nelfinavir (NFV) and correlation to efficacy in pediatric patients (abstract 348). Presented at: 1st International AIDS Society Conference on HIV Pathogenesis and Treatment, Buenos Aires, Argentina, July 8\u201311, 2001."},{"key":"bibr15-aph.1C335","unstructured":"15 Acosta EP, Nachman S, Wiznia A, Turner M, Sommadossi JP, Yogev R. Pharmacokinetic (PK) evaluation of nelfinavir (NFV) in combination with nevirapine (NVP) or ritonavir (RTV) in HIV-infected children\u2014PACTG 403 (abstract 1642). Presented at: 40th International Conference on Antimicrobial Agents and Chemotherapy, Toronto, Ontario, Canada, September 17\u201320, 2000."},{"key":"bibr16-aph.1C335","unstructured":"16 Litalien C, Ciaquinto C, Faye A, Mechinaud F, Grosch I, Compagnucci A, et al. Nelfinavir doses should be increased in infants less than 3 months (abstract MoPeB2213). Presented at: XIII International AIDS Conference, Durban, Republic of South Africa, July 9\u201314, 2000."},{"key":"bibr17-aph.1C335","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.162.9.985"},{"key":"bibr18-aph.1C335","unstructured":"18 Capparelli EV, Burchett S, Kovacs A, Khoury M, Carey V, Smith E, et al. Nelfinavir (NFV) pharmacokinetics in combination with ritonavir (RTV) in infants and children with advanced HIV disease (abstract 661). Presented at: 7th Conference on Retroviruses and Opportunistic Infections, San Francisco, January 30-February 2, 2000."},{"key":"bibr19-aph.1C335","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200201040-00010"},{"key":"bibr20-aph.1C335","doi-asserted-by":"publisher","DOI":"10.1086\/313548"},{"key":"bibr21-aph.1C335","unstructured":"21 Bergshoeff AS, Fraaij PL, van Rossum AM, Wolfs TF, Geelen SP, de Groot R, et al. Nelfinavir pharmacokinetics in children: who are at risk for subtherapeutic plasma levels? (abstract TuPeB4557). Presented at: XIVth International Aids Conference, Barcelona, Spain, July 7\u201312, 2002."},{"key":"bibr22-aph.1C335","unstructured":"22 Flexner C. Steady-state pharmacokinetic interactions between ritonavir (RTV), nelfinavir (NFV) and the nelfinavir active metabolite M8 (AG1402) (abstract 42265). Presented at: 12th World AIDS Conference, Geneva, Switzerland, June 28\u2013July 3, 1998."},{"key":"bibr23-aph.1C335","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.126178"}],"container-title":["Annals of Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1345\/aph.1C335","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1345\/aph.1C335","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1345\/aph.1C335","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:06:55Z","timestamp":1777374415000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1345\/aph.1C335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,4]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2003,4]]}},"alternative-id":["10.1345\/aph.1C335"],"URL":"https:\/\/doi.org\/10.1345\/aph.1c335","relation":{},"ISSN":["1060-0280","1542-6270"],"issn-type":[{"value":"1060-0280","type":"print"},{"value":"1542-6270","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,4]]}}}