Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abacavir (1592U89), a nucleoside reverse transcriptase inhibitor with in vitro activity against human immunodeficiency virus type-1 (HIV-1), has been evaluated for efficacy and safety in combination regimens with other nucleoside analogs, including zidovudine (ZDV) and lamivudine (3TC). To evaluate the potential pharmacokinetic interactions between these agents, 15 HIV-1-infected adults with a median CD4(+) cell count of 347 cells/mm3 (range, 238 to 570 cells/mm3) were enrolled in a randomized, seven-period crossover study. The pharmacokinetics and safety of single doses of abacavir (600 mg), ZDV (300 mg), and 3TC (150 mg) were evaluated when each drug was given alone or when any two or three drugs were given concurrently. The concentrations of all drugs in plasma and the concentrations of ZDV and its 5'-glucuronide metabolite, GZDV, in urine were measured for up to 24 h postdosing, and pharmacokinetic parameter values were calculated by noncompartmental methods. The maximum drug concentration (Cmax), the area under the concentration-time curve from time zero to infinity (AUC0-infinity), time to Cmax (Tmax), and apparent elimination half-life (t1/2) of abacavir in plasma were unaffected by coadministration with ZDV and/or 3TC. Coadministration of abacavir with ZDV (with or without 3TC) decreased the mean Cmax of ZDV by approximately 20% (from 1.5 to 1.2 microg/ml), delayed the median Tmax for ZDV by 0.5 h, increased the mean AUC0-infinity for GZDV by up to 40% (from 11.8 to 16.5 microg. h/ml), and delayed the median Tmax for GZDV by approximately 0.5 h. Coadministration of abacavir with 3TC (with or without ZDV) decreased the mean AUC0-infinity for 3TC by approximately 15% (from 5.1 to 4.3 microg. h/ml), decreased the mean Cmax by approximately 35% (from 1.4 to 0.9 microg/ml), and delayed the median Tmax by approximately 1 h. While these changes were statistically significant, they are similar to the effect of food intake (for ZDV) or affect an inactive metabolite (for GZDV) or are relatively minor (for 3TC) and are therefore not considered to be clinically significant. No significant differences were found in the urinary recoveries of ZDV or GZDV when ZDV was coadministered with abacavir. There was no pharmacokinetic interaction between ZDV and 3TC. Mild to moderate headache, nausea, lymphadenopathy, hematuria, musculoskeletal chest pain, neck stiffness, and fever were the most common adverse events reported by those who received abacavir. Coadministration of ZDV or 3TC with abacavir did not alter this adverse event profile. The three-drug regimen was primarily associated with gastrointestinal events. In conclusion, no clinically significant pharmacokinetic interactions occurred between abacavir, ZDV, and 3TC in HIV-1-infected adults. Coadministration of abacavir with ZDV or 3TC produced mild changes in the absorption and possibly the urinary excretion characteristics of ZDV-GZDV and 3TC that were not considered to be clinically significant. Coadministration of abacavir with ZDV and/or 3TC was generally well tolerated and did not produce unexpected adverse events.
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PMID:Single-dose pharmacokinetics and safety of abacavir (1592U89), zidovudine, and lamivudine administered alone and in combination in adults with human immunodeficiency virus infection. 1039 Feb 27

A 27-year-old pregnant woman was admitted to a local hospital because of headache, nausea, and general fatigue. Her blood examination showed leukocytosis, anemia, and thrombocytopenia. She was referred to our hospital in March 1998. Her bone marrow was normocellular with an excess of blasts (89.1%, peroxidase stain(-), PAS stain(-)) that displayed a positive immunophenotype for CD2, CD4, CD5, CD7, CD34, CD38, and CD71. Chromosome analysis revealed complex abnormal karyotypes. The patient was given a diagnosis of acute lymphoblastic leukemia associated with central nervous system and breast infiltration, and received induction chemotherapy during the second trimester of her pregnancy. After she achieved complete remission, a cesarean section was performed, and a healthy baby delivered. Our experience in this case demonstrated that combination chemotherapy during the second trimester of pregnancy is feasible.
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PMID:[Acute lymphoblastic leukemia with breast infiltration during the second trimester of pregnancy and followed by successful delivery]. 1049 40

Pentostatin (Nipent; SuperGen, San Ramon, CA), which is highly lymphocytotoxic, is an active agent in hairy cell leukemia. We therefore initiated a trial of this agent in T-cell lymphomas. Pentostatin was administered at a dose of 3.75 or 5.0 mg/m2/d intravenously for 3 days every 3 weeks to heavily pretreated patients with cutaneous and peripheral T-cell lymphomas. To date, there are 24 evaluable patients in the trial. Seventeen of these individuals have responded (complete or partial remission). The most common toxicities included granulocytopenia, nausea, renal insufficiency, CD4 suppression, and delayed herpes zoster. Pentostatin is an active agent in this group of diseases and merits further exploration.
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PMID:Pentostatin (Nipent) in T-cell lymphomas. 1087 55

Abacavir (formerly 1592U89) is a carbocyclic nucleoside analog with potent anti-human immunodeficiency virus (anti-HIV) activity when administered alone or in combination with other antiretroviral agents. The population pharmacokinetics and pharmacodynamics of abacavir were investigated in 41 HIV type 1 (HIV-1)-infected, antiretroviral naive adults with baseline CD4(+) cell counts of >/=100/mm(3) and plasma HIV-1 RNA levels of >30,000 copies/ml. Data for analysis were obtained from patients who received randomized, blinded monotherapy with abacavir at 100, 300, or 600 mg twice-daily (BID) for up to 12 weeks. Plasma abacavir concentrations from sparse sampling were analyzed by standard population pharmacokinetic methods, and the effects of dose, combination therapy, gender, weight, and age on parameter estimates were investigated. Bayesian pharmacokinetic parameter estimates were calculated to determine the peak concentration of abacavir in plasma (C(max)) and the area under the concentration-time curve from time zero to infinity (AUC(0-infinity)) for individual subjects. The pharmacokinetics of abacavir were dose proportional over the 100- to 600-mg dose range and were unaffected by any covariates. No significant correlations were observed between the incidence of the five most common adverse events (headache, nausea, diarrhea, vomiting, and malaise or fatigue) and AUC(0-infinity). A significant correlation was observed between C(max) and nausea by categorical analysis (P = 0.019), but this was of borderline significance by logistic regression (odds ratio, 1.45; 95% confidence interval, 0.95 to 2.32). The log(10) time-averaged AUC(0-infinity) minus baseline (AAUCMB) values for HIV-1 RNA and CD4(+) cell count correlated significantly with C(max) and AUC(0-infinity), but with better model fits for AUC(0-infinity). The increase in AAUCMB values for CD4(+) cell count plateaued early for drug exposures that were associated with little change in AAUCMB values for plasma HIV-1 RNA. There was less than a 0.4 log(10) difference over 12 weeks in the HIV-1 RNA levels with the doubling of the abacavir AUC(0-infinity) from 300 to 600 mg BID dosing. In conclusion, pharmacodynamic modeling supports the selection of abacavir 300 mg twice-daily dosing.
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PMID:Population pharmacokinetics and pharmacodynamic modeling of abacavir (1592U89) from a dose-ranging, double-blind, randomized monotherapy trial with human immunodeficiency virus-infected subjects. 1089 75

A 40-year-old HIV-infected woman developed nausea, vomiting, and epigastric pain and died following her third dose (per study protocol) of interleukin (IL)-2. Her HIV infection was diagnosed in 1996. Her last CD4 cell count was 390/microL, and her viral load was negligible (as of November 28, 1998). She had no known general risk factors for thrombosis other than HIV infection, injection drug abuse, and antiretroviral therapy with indinavir. Abdominal films showed no sign of mechanical obstruction but a generalized gas distention of the bowel, which was suggestive of paralytic ileus. Autopsy revealed dilation of the small bowel with extensive necrosis and hemorrhage involving all the segments. The superior and inferior mesenteric arteries revealed severe atherosclerosis. The stenotic celiac artery was occluded by a recent thrombus at the aortic ostium. Clinicians need to be aware of the potential for thrombosis and accelerated atherosclerosis in HIV-infected patients. Both injection drug abuse and protease inhibitors, such as indinavir, have been shown to be risk factors for thrombosis. However, it is likely IL-2 contributed to the severe thrombosis in this patient, although definitive proof is lacking. An acute awareness of intestinal infarction in HIV-infected patients is warranted.
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PMID:Case report. Intestinal infarction due to vascular catastrophe in an HIV-infected patient. 1118 43

The nucleoside reverse transcriptase inhibitor 3TC (lamivudine) appears to induce unusually prolonged HIV suppression when used in combination with AZT, according to the results of four randomized clinical trials. The studies showed that 3TC and AZT had similar antiviral effects when used alone. However, investigators observed a substantial, prolonged increase in CD4 counts and a significant decrease in HIV RNA when the drugs were administered simultaneously. These benefits persisted in all study groups for the 24-week study period, and in several for the six-month follow-up period as well. The combination was well-tolerated by nearly 1000 AZT-naive and AZT-experienced subjects enrolled in these trials, with the most common adverse effects being nausea, vomiting and headaches. A possible explanation for the antiviral effect is suggested by the mutation at HIV codon 184 that is frequently observed in virions exposed to 3TC for extended periods of time. In vitro studies have shown that this mutation confers 3TC resistance. It may also counteract other mutations that would normally lead to AZT resistance, therefore enabling virions exposed to both drugs to remain effectively susceptible to AZT.
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PMID:Combination 3TC/AZT therapy shows promise. 1136 92

It was reported at the 1995 Second National Retrovirus Conference that AIDS has now surpassed unintentional injury as the leading cause of death for male Americans between the ages of 25 to 44, and for women, AIDS is fourth behind unintentional injury. A study of multidrug resistant tuberculosis that showed improved survival rates as long as appropriate therapy began within four weeks of diagnosis was also presented. The current recommendation is to consider the PPD skin test positive in persons with HIV if the bump that appears is over five millimeters in diameter. A new ganciclovir implant study demonstrated the implant's effectiveness in preventing CMV disease progression with low rates of complications, suggesting implants should probably replace intravenous ganciclovir as maintenance therapy. Another study demonstrated the effectiveness of cidofovir as a treatment for CMV infection, indicating that cidofovir was appropriate as a salvage therapy for those failing ganciclovir and foscarnet. In vitro studies involving Taxol and Kaposi's sarcoma (KS) show partial responses (55 percent), and some disease stabilization (40 percent). Four of five patients with pulmonary KS responded with clearance of tumor lesions. The first randomized trial involving Loviride with zidovudine has shown a sustained increase in CD4 cells with headache, nausea, and diarrhea as the most common side effects. Preliminary assessments reveal a reduction in viral load using the combination as opposed to monotherapy. Additional Loviride combination trials are being planned in Europe.
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PMID:Second National Retrovirus conference: a further report. 1136 59

AIDS patients over age twelve, with CD4 counts of fifty or less, and who meet other health status-related criteria will be eligible to participate in the Abbott Laboratories' ritonavir lottery program. About 2,000 patients worldwide with advanced AIDS will participate. A new drug formulation may help diminish commonly seen adverse effects of ritonavir, such as nausea and diarrhea. There are also a significant number of other drugs which have adverse interactions with ritonavir.
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PMID:2000 PWAs to get ritonavir via expanded access. 1136 98

The Food and Drug Administration (FDA) approved the first protease inhibitor, saquinavir, for combination treatment with approved nucleoside analogs in adults with advanced HIV. However, it denied the use of saquinavir as a monotherapy. Protease inhibitors prevent infected cells from reproducing viral particles. All saquinavir studies have used a dose of 600mg 3 times per day. Another formulation of saquinavir and higher dosages of the present formulation are being tested to increase the bioavailability. In AZT-naive patients, a combination of saquinavir and AZT produces better improvements in CD4 counts and in viral load reduction compared to either of the drugs alone. In patients with extensive prior AZT therapy, saquinavir in combination with ddC provided greater and longer surrogate marker benefits compared to either drug alone. Saquinavir also improved the activity of ddC plus AZT. The most common side effects were diarrhea and nausea. Altogether, only four percent of patients receiving saquinavir had side effects. Toxicity was not increased when saquinavir was added to AZT and ddC. Cross resistance to other PIs has been found, so the use of saquinavir may limit the benefits of future PIs.
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PMID:No tease this time--pros and cons of a long-awaited anti-HIV drug. 1136 18

Glaxo Wellcome is offering an expanded access program for abacavir (Ziagen, formerly 1592) to HIV-positive patients who are not benefiting from their current combination therapy. In a dramatic departure from the usual entry criteria, the abacavir eligibility criteria require no specific CD4 cell count or viral load. To qualify, volunteers must be on a failing regimen, unable to tolerate standard therapies, and a physician must verify that another drug combination would not be viable. Patients are urged to switch to a regimen of at least two new drugs based on U.S. government treatment guidelines. Similar programs are available for the anti-HIV drugs efavirenz (Sustiva) and adefovir dipivoxil (Preveon). People using abacavir, a nucleoside analog, may experience side effects such as headache, nausea, and vomiting. If a hypersensitivity reaction develops, patients must stop the treatment. Taking the drug after experiencing an adverse reaction can be life threatening.
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PMID:Glaxo opens broad expanded access program for abacavir (Ziagen). 1136 71


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