Lopinavir.
Lopinavir is a protease inhibitor with high specificity for HIV-1 protease. Ritonavir strongly inhibits lopinavir metabolism; coadministration of lopinavir and ritonavir in healthy volunteers increased the area under the lopinavir plasma concentration-time curve >100-fold. Trough plasma concentration: antiviral 50% effective concentration ratio for lopinavir was >75 for wild-type HIV at the dose used in clinical trials, compared to values of < or = 4 for other commonly used protease inhibitors. Coformulated lopinavir and ritonavir (lopinavir/ ritonavir) 400/100mg twice daily for 48 weeks suppressed HIV replication in significantly more antiretroviral-naive patients than nelfinavir 750mg 3 times daily (all patients also received stavudine and lamivudine). Suppression of viral replication was observed in most protease inhibitor-experienced patients with lopinavir/ ritonavir (400/100, 400/200 or 533/133mg twice daily for 48 or 96 weeks) in combination with > or = 2 nucleoside reverse transcriptase inhibitors (NRTIs) and either efavirenz or nevirapine. 48 weeks of treatment with twice daily lopinavir/ ritonavir (230/57.5 or 300/75 mg/m2 for the first 12 weeks and then 300/75 mg/m2) in combination with 1 or2 NRTIs, with or without nevirapine, suppressed viral replication in the majority of antiretroviral-naive and -experienced paediatric patients (aged 6 months to 12 years). Diarrhoea, nausea and asthenia were the most frequently reported adverse effects in patients receiving lopinavir/ritonavir-based regimens. Elevated total cholesterol, triglyceride and hepatic enzyme levels were also reported.
Hurst
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Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail@adis.co.nz
Faulds
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D000328:Adult; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007223:Infant; D061466:Lopinavir; D015394:Molecular Structure; D011744:Pyrimidinones / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use
D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir