Biomedical subjects

A Bardsley-Elliot

Publications and source records attributed to A Bardsley-Elliot.

3 recordsLinked to original sources

PubMed2000

Nelfinavir: an update on its use in HIV infection.

UNLABELLED: Nelfinavir is one of several currently available protease inhibitors used to limit viral replication and improve immune function in HIV-infected individuals. It is administered in combination with other antiretroviral agents. Nelfinavir has been evaluated as first-line therapy with nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-naive patients, or as an additional antiretroviral agent in protease inhibitor-naive patients already receiving NRTIs. These studies have shown good efficacy in terms of HIV viral load reduction and increased CD4+ cell counts. When used in combination with NRTIs, nelfinavir 1250 mg twice daily produced similar results to 750 mg 3 times daily. The more convenient twice-daily dosage schedule, which is now approved in the US, may be beneficial in improving patient adherence to therapy. Nelfinavir has also been used successfully in combination with non-nucleoside reverse transcriptase inhibitors and/or other protease inhibitors, with or without NRTIs. Resistance to nelfinavir has been observed in vitro and in clinical isolates from patients experiencing insufficient or waning viral suppression during treatment. Nelfinavir primarily selects for the D30N mutation, which is not seen with other protease inhibitors, and alone does not cause resistance to other protease inhibitors in vitro. Several studies have shown that patients who experience virological failure while receiving nelfinavir can respond to salvage therapy with other protease inhibitors. Diarrhoea is the most frequent adverse event in patients receiving nelfinavir-based combination therapy, but was generally mild and resulted in minimal discontinuation of therapy in clinical trials. Diarrhoea can usually be controlled with drugs that slow gastrointestinal motility. Metabolic disturbances associated with protease inhibitor use (hypercholesterolaemia, hyperglycaemia and lipodystrophy) have also been reported with nelfinavir. Nelfinavir is associated with a number of clinically significant drug interactions and coadministration of some drugs (e.g. astemizole, cisapride, triazolam) is contraindicated. Coadministration of nelfinavir with other protease inhibitors generally resulted in favourable pharmacokinetic interactions (usually increased area under the concentration-time curve for both drugs). CONCLUSION: Nelfinavir, in combination with reverse transcriptase inhibitors and/or other protease inhibitors, is effective in limiting HIV replication and increasing CD4+ cell counts in HIV-infected adults and children. The convenience of its dosage administration, the low incidence of adverse events, and the potential for salvage therapies indicate that nelfinavir (as part of combined antiretroviral therapy regimens) should be considered as a first-line option in protease inhibitor-naive patients and in those unable to tolerate other protease inhibitors.

Adult↗

PubMed1999

Oseltamivir.

Oseltamivir is the oral prodrug of GS4071, a selective inhibitor of influenza A and B viral neuraminidase. After absorption from the gastrointestinal tract oseltamivir is efficiently converted to GS4071, which is maintained at high and sustained concentrations in plasma. Based on studies in rats and ferrets, GS4071 appears to be effectively distributed to all tissues, including major sites of infection in the upper and lower respiratory tracts. Oral oseltamivir was an effective treatment in naturally occurring influenza when administered within 36 hours of symptom onset, reducing both the duration and severity of symptoms and the incidence of secondary complications in influenza-infected patients enrolled in 2 large placebo-controlled, double-blind trials. Prophylactic oral administration of oseltamivir was effective in reducing the incidence of influenza illness according to pooled data from 2 large placebo-controlled, double-blind trials of healthy nonimmunised volunteers during periods of seasonal influenza activity. The reported incidence of viral resistance to GS4071 was low in clinical isolates from oseltamivir treatment studies. All known GS4071 resistant genotypes are growth disadvantaged and display significantly reduced infectivity in animals. Oseltamivir was well tolerated in human volunteers and patients in clinical trials. Treatment-related adverse events (primarily gastrointestinal) were mild and transient in nature.

Acetamides↗

PubMedDate not supplied

Nevirapine: a review of its use in the prevention and treatment of paediatric HIV infection.

UNLABELLED: Nevirapine is a highly specific inhibitor of HIV-1 reverse transcriptase (RT), an important therapeutic target for the treatment of HIV infection. It was the first non-nucleoside RT inhibitor (NNRTI) to be approved for use in HIV-infected individuals, including children. Nevirapine inhibits replication of multiple HIV-1 strains and clinical isolates in cultured human T cells, but has no activity against other retroviral RTs (including HIV-2 RT) or endogenous human DNA polymerases. Monotherapy with nevirapine rapidly selects for high level drug resistance conferred by a single amino acid substitution in the HIV RT gene. The pattern of resistance mutations selected by nevirapine overlaps with those of other NNRTIs, but is distinct from those of nucleoside analogue RT inhibitors and protease inhibitors. The pharmacokinetics of nevirapine are characterised by rapid and nearly complete oral absorption, an apparently even distribution throughout all organs and tissues in the body, and a long elimination half-life. Nevirapine is both metabolised by and induces the activity of cytochrome P450 isoenzymes. Caution is required when coadministering nevirapine with other drugs metabolised by this system, including HIV protease inhibitors. As a single dose therapy given to pregnant women in labour and to neonates shortly after birth, nevirapine reduced the rate of perinatal HIV transmission by 47% compared with a short course of intrapartum and neonatal zidovudine in a randomised trial in breastfeeding women in Uganda. Nevirapine was more cost effective than zidovudine-based regimens for the prevention of perinatal HIV transmission in a cost-effectiveness model in sub-Saharan Africa. Nevirapine has shown antiretroviral efficacy as part of combination therapy with zidovudine and either didanosine or lamivudine in small numbers of paediatric patients in phase I/II trials. Triple therapy of nevirapine, zidovudine and didanosine was moderately effective in a randomised, nonblind trial in patients with advanced disease. The most frequent adverse event associated with nevirapine is rash, which occasionally develops into severe rash or Stevens-Johnson syndrome. Elevations in liver enzyme levels can occasionally lead to severe complications in patients receiving multiple dose nevirapine. CONCLUSION: Single dose nevirapine appears to be the most cost-effective of available options for the prevention of perinatal HIV transmission suitable for use in developing countries. In addition, preliminary clinical trial data suggest that nevirapine adds to the efficacy of combination therapy for the treatment of HIV infection in infants and children, and is reasonably well tolerated.

Anti-HIV Agents↗