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Biomedical subjects

H B Fung

Publications and source records attributed to H B Fung.

6 recordsLinked to original sources
PubMed2001

Linezolid: an oxazolidinone antimicrobial agent.

BACKGROUND: Linezolid is the first oxazolidinone anti-infective agent marketed in the United States. It is indicated for the treatment of nosocomial pneumonia, complicated skin and skin-structure infections caused by methicillin-sensitive or methicillin-resistant Staphylococcus aureus and other susceptible organisms, and vancomycin-resistant Enterococcus faecium infections. It also is indicated for the treatment of uncomplicated skin and skin-structure infections caused by methicillin-sensitive S. aureus or Streptococcus pyogenes, and community-acquired pneumonia caused by penicillin-sensitive Streptococcus pneumoniae. OBJECTIVE: This article reviews the pharmacologic properties and clinical usefulness of linezolid. METHODS: Using the terms linezolid, PNU-100766, and oxazolidinone, we performed a literature search of the following databases: MEDLINE (1966 to September 2000), HealthSTAR (1993 to September 2000), Iowa Drug Information Service (1966 to September 2000), International Pharmaceutical Abstracts (1970 to September 2000), PharmaProjects (January 2000 version), and meeting abstracts of the Infectious Diseases Society of America and the Interscience Conference on Antimicrobial Agents and Chemotherapy (1996 to 2000). RESULTS: Linezolid has a unique structure and mechanism of action, which targets protein synthesis at an exceedingly early stage. Consequently, cross-resistance with other commercially available antimicrobial agents is unlikely. It is primarily effective against gram-positive bacteria. To date, resistance to linezolid has been reported in patients infected with enterococci. The pharmacokinetic parameters of linezolid in adults are not altered by hepatic or renal function, age, or sex to an extent requiring dose adjustment. Linezolid is metabolized via morpholine ring oxidation, which is independent of the cytochrome P450 (CYP450) enzyme system; as a result, linezolid is unlikely to interact with medications that stimulate or inhibit CYP450 enzymes. Compassionate-use trials and other clinical studies involving mainly adult hospitalized patients with gram-positive infections have shown that linezolid administered intravenously or orally is effective in a variety of nosocomial and community-acquired infections, including those caused by resistant gram-positive organisms. Reported adverse effects include thrombocytopenia. diarrhea, headache, nausea, vomiting, insomnia, constipation, rash, and dizziness. Preliminary pharmacoeconomic data indicate that a significantly higher percentage of patients receiving linezolid therapy versus comparator could be discharged from the hospital by day 7 (P = 0.005). CONCLUSIONS: Linezolid appears to be effective while maintaining an acceptable tolerability profile. Due to the risk of bacterial resistance, linezolid should be reserved for the treatment of documented serious vancomycin-resistant enterococcal infections.

Acetamides↗
PubMed2000

Amprenavir: a new human immunodeficiency virus type 1 protease inhibitor.

OBJECTIVE: This paper reviews the pharmacologic properties and clinical usefulness of amprenavir, a new human immunodeficiency virus type 1 (HIV-1) protease inhibitor. BACKGROUND: Amprenavir, the most recent HIV-1 protease inhibitor to receive marketing approval from the US Food and Drug Administration, is a potent competitive inhibitor of HIV-1 protease and a relatively weak inhibitor of HIV-2 protease. Inhibition of the HIV-1 protease enzyme results in immature and noninfectious viral particles. Amprenavir is rapidly absorbed following oral administration. The time to peak concentration (Tmax) in adults is between 1 and 2 hours, the area under the plasma concentration versus time curve is roughly proportional to the dose, the half-life is approximately 8 hours, and the volume of distribution is approximately 430 L. The Tmax in children 4 to 12 years of age is between 1.1 and 1.4 hours. The bioavailability of the solution is 86% relative to the capsule formulation. It is metabolized by the cytochrome P-450 isozyme CYP3A4 and to a lesser extent by CYP2D6 and CYP2C9. METHODS: We searched MEDLINE (1966 to January 2000), AIDSLINE (1980 to January 2000), International Pharmaceutical Abstracts (1970 to January 2000), PharmaProjects (January 2000 version), and Web sites of major HIV/acquired immunodeficiency syndrome conferences for appropriate published references (1996 to February 2000). RESULTS: Data reported to date indicate that amprenavir is efficacious in the treatment of HIV disease in patients with primary HIV infection, antiretroviral-naïve patients, protease inhibitor-naïve patients, protease inhibitor-experienced patients, and pediatric patients. Adverse effects were usually of early onset (range, 2 to 21 days) and transient (range, 3 to 46 days), although the incidence of metabolic abnormalities such as lipodystrophy, hyperlipidemia, and diabetes mellitus has not yet been defined. Amprenavir should be avoided in patients with a known sulfonamide allergy. Concomitant use of other medications that are CYP3A4 inducers or inhibitors should be done cautiously and only if the potential benefit clearly outweighs potential risk. The dose should be reduced in patients with significant hepatic impairment (Child-Pugh score, > or = 5). Amprenavir probably should not be administered with rifabutin, rifampin, astemizole, midazolam , triazolam, bepridil, dihydroergotamine, ergotamine, or cisapride. The recommended adult dose is 1200 mg twice daily. For patients between 4 and 12 years of age or between 13 and 16 years of age who weigh < 50 kg, the recommended dosage of the capsule form is 20 mg/kg (22.5 mg/kg for oral solution) twice daily or 15 mg/kg (17 mg/kg for oral solution) 3 times a day to a maximum dose of 2400 mg (2800 mg for oral solution). Patients should not take vitamin E supplements because amprenavir is formulated with a large amount of vitamin E (109 IU/capsule and 46 IU/mL oral solution) to improve oral absorption. Amprenavir may be administered with or without food, but a high-fat meal (> 67 g fat) should be avoided. CONCLUSIONS: Published clinical data are limited, but amprenavir appears to be efficacious and generally well tolerated in patients with HIV infection. Pharmacoeconomic data are not yet available. The introduction of amprenavir appears to be important, since it provides an additional treatment option as a component of both initial and salvage combination therapies for patients with HIV.

Anti-HIV Agents↗
PubMed1999

Selective cyclooxygenase-2 inhibitors for the treatment of arthritis.

The purpose of this paper is to review the rationale for a new class of nonsteroidal anti-inflammatory drugs (NSAIDs) known as selective cyclooxygenase (COX)-2 inhibitors and to present preliminary clinical data on 2 COX-2 inhibitors that are approved for use in the United States. The primary mechanism of NSAIDs in the treatment of inflammation is the inhibition of COX, which exists in 2 forms. COX-I appears to regulate many normal physiologic functions, and COX-2 mediates the inflammatory response. Theoretically, an NSAID that inhibits COX-2 selectively should decrease inflammation but not influence normal physiologic functions and thus should cause fewer gastrointestinal side effects. Preliminary data suggest that celecoxib, a highly selective COX-2 inhibitor, is superior to placebo and similar to traditional NSAIDs in the short-term treatment of pain due to osteoarthritis, although it has been associated with adverse effects such as headache, change in bowel habits, abdominal discomfort, and dizziness. Celecoxib also has been shown to be as effective as traditional NSAIDs in the treatment of rheumatoid arthritis, but it may cause fewer adverse effects, including endoscopically documented ulcers. Celecoxib is metabolized in the liver by the cytochrome P-450 isozyme CYP2C9, and thus serious drug interactions are possible. In the treatment of osteoarthritis, rofecoxib has been shown to be as effective as traditional NSAIDs and may cause fewer endoscopically documented ulcers, but its complete adverse-effect profile is not known. Until the selective COX-2 inhibitors are widely used and more clinical as well as pharmacoeconomic studies are published, the exact role of COX-2 therapy cannot be determined. words: cyclooxygenase, celecoxib, rofecoxib, rheumatoid arthritis, osteoarthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Indinavir-associated maculopapular eruption.

Indinavir-associated adverse dermatologic reactions are rare but do occur. A 39-year-old man who was positive for the human immunodeficiency virus and had no known allergy, developed an erythematous, maculopapular eruption several hours after switching to a new triple-drug regimen consisting of stavudine, didanosine, and indinavir. The eruption completely resolved 2 weeks after he discontinued the antiretroviral combination. To preserve future treatment options, the patient was sequentially rechallenged with each agent and confirmed indinavir as the cause. The patient tolerated and responded to a new combination of stavudine, didanosine, and nelfinavir. The rapid onset of the adverse reaction suggested that it might have been immunoglobulin-E mediated. No cross-sensitivity between indinavir and nelfinavir was apparent.

Adult↗
PubMedDate not supplied

Treatment regimens for patients with toxoplasmic encephalitis.

Toxoplasma gondii is an obligate intracellular parasitic protozoan that infects a variety of warm-blooded animals, including humans. Infection is usually asymptomatic in immunocompetent individuals but may be devastating in immunocompromised individuals such as those with acquired immunodeficiency syndrome (AIDS). Clinical manifestations of infection in immunocompromised patients include the development of encephalitis. It has been estimated that approximately 30% of patients with AIDS who are latently infected will eventually develop toxoplasmic encephalitis. The most common regimen used to treat toxoplasmic encephalitis is a combination of pyrimethamine 50 to 100 mg/d and sulfadiazine 4 to 8 g/d, with or without folinic acid 10 mg/d. This regimen, however, commonly leads to adverse effects or relapses. Other pharmacologic approaches include the use of clindamycin rather than sulfadiazine, the macrolide antibiotics, atovaquone, 5-fluorouracil, trimethoprim/sulfamethoxazole, minocycline or doxycycline, trimetrexate with folinic acid, dapsone, rifabutin, pentamidine, and diclazuril. None of these alternative regimens has been proven to be more effective than the standard pharmacologic therapy. An evolving approach is the use of immunotherapy, such as interleukin-2, -6, and -12; interferon-gamma; and alpha-tumor necrosis factor. Restoring a competent immune system may be the only cure for toxoplasmosis and other opportunistic infections.

AIDS-Related Opportunistic Infections↗