Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tipranavir (TPV) is a non-peptidic protease inhibitor belonging to the class of 4-hydroxy-5,6-dihydro-2-pyrones, which exhibits potent and specific activity against HIV type I (HIV-1) and 2 (HIV-2). Clinically effective plasma levels of TPV are achieved by concomitant administration of ritonavir (RTV). Therefore, TPV has been coadministered with RTV in clinical trials. TPV has demonstrated antiviral activity against HIV-1 isolates that are resistant to reverse-transcriptase and selected peptidic protease inhibitors. Therefore, TPV is emerging as one of the newer drugs in the armamentarium against HIV-1 in patients demonstrating multi-drug resistance. TPV administered orally to humans exhibits linear pharmacokinetics at doses of 100 - 2000 mg. Steady-state plasma levels are attained within 7 days of initiating multiple dosing. The half-life of the drug is approximately 6 h at steady-state. The plasma concentration is lower with repeated dosing than predicted from single-dose studies due to induction of the cytochrome p450 3A4 isoform of the liver microsomal enzyme system. Phase II clinical trials have shown that the administration of TPV and RTV in combination is safe and generally well-tolerated in HIV-1-infected adults. Phase III trials are underway to compare the efficacy of this drug versus other antiretroviral regimens. Gastrointestinal toxicity has been described with TPV, the most frequently reported side effects being diarrhoea, nausea, vomiting and abdominal pain. There is no known evidence of teratogenicity or effect on fertility. TPV dosed twice-daily, in the range of 500 - 1250 mg and combined with 100 - 200 mg of RTV has been shown to substantially and durably reduce viral load in HIV-1-infected drug-naive and experienced patients.
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PMID:Tipranavir: a novel non-peptidic protease inhibitor for the treatment of HIV infection. 1458 57

The efficacy, safety, and pharmacokinetics of three doses of tipranavir/ritonavir (TPV/r) in highly treatment-experienced human immunodeficiency virus (HIV)-1-infected patients with protease inhibitor (PI)-resistant isolates were evaluated. A 24-week multicenter, double-blind, randomized, dose-finding trial was conducted. All patients were three-drug class experienced and had taken at least two PI-based regimens. All had at least one primary PI mutation and had plasma HIV-RNA > 1000 copies/ml. Patients remained on their background non-PI antiretroviral medications for the first 14 days. After this 14-day period of functional TPV/r monotherapy, the background antiretroviral medications were optimized based on treatment history and the screening genotype. A total of 216 patients were randomized. All groups [TPV/r 500 mg/100 mg (n = 73), 500 mg/200 mg (n = 72), and 750 mg/200 mg (n = 71) twice daily] achieved an approximate 1 log10 reduction in the median HIV-RNA at week 2. A significant reduction was sustained through 24 weeks in the TPV/r 500 mg/200 mg and 750 mg/200 mg groups. The 500 mg/200 mg dose achieved optimal median TPV trough concentrations and lower interpatient variability. The most frequently reported adverse events (AEs) were diarrhea, nausea, vomiting, fatigue, and headache. The TPV/r 750 mg/200 mg group had the highest rate of grade 3 or 4 laboratory abnormalities and study discontinuations due to AEs. All doses of TPV/r tested in this study were associated with HIV-1 viral load reductions through 24 weeks. The 500 mg/200 mg dose achieved the best efficacy, safety, and pharmacokinetic profile in this highly treatment-experienced population and was selected for the pivotal phase 3 studies.
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PMID:Efficacy and safety of three doses of tipranavir boosted with ritonavir in treatment-experienced HIV type-1 infected patients. 1726 50