Therapeutic Drug Monitoring in the Treatment of TuberculosisPeloquin, Charles
doi: 10.2165/00003495-200262150-00001pmid: 12381217
Therapeutic drug monitoring (TDM) is a standard clinical technique used for many disease states, including many infectious diseases. As for these other conditions, the use of TDM in the setting of tuberculosis (TB) allows the clinician to make informed decisions regarding the timely adjustment of drug therapy. Such adjustments may not be required for otherwise healthy individuals who are responding to the standard, four-drug TB regimens. However, some patients are slow to respond to treatment, have drug-resistant TB, are at risk of drug-drug interactions or have concurrent disease states that significantly complicate the clinical situation. Such patients may benefit from TDM and early interventions may preclude the development of further drug resistance.
HMG- CoA Reductase Inhibitors as ImmunomodulatorsRaggatt, Liza; Partridge, Nicola
doi: 10.2165/00003495-200262150-00002pmid: 12381218
The benefit of HMG-CoA reductase inhibitors (statins) to the cardiovascular system is now well established and these drugs are being used extensively to treat hypercholesterolaemia clinically. However, as clinical outcomes become available it appears that statins are proving more beneficial than expected and thus it is being proposed that the actions of statins go beyond their ability to lower serum cholesterol levels. The report that statins can interact directly with lymphocyte function-associated antigen (LFA)-l and prevent it engaging with the intracellular adhesion molecule (ICAM)-1 receptor on T cells is a novel mechanism of statin action and provides convincing evidence that these compounds can regulate biological systems other than by the cholesterol synthesis pathway. Immunosuppression to prevent organ transplant rejection is one application for which statins are currently being assessed. The clinical evidence is conflicting and does not convincingly reflect whether statins are beneficial as immunomodulators. However, in vivo studies investigating the cellular actions of statins have identified two mechanisms by which statins can potentially modulate an in vivo immune response. Firstly, statins regulate inducible class II major histocompatibility complex (MHC) expression on macrophages and endothelial cells. Secondly, statins can inhibit LFA-1 adhesion to ICAM-1 and thus regulate T cell activation. These findings suggest that statins have the potential to regulate an immune response in vivo and that more investigation is essential in order to explain the opposing clinical data.
Prevention of Perinatal HIV TransmissionKourtis, Athena
doi: 10.2165/00003495-200262150-00004pmid: 12381220
Significant progress has been made in the battle against transmission of HIV-1 from mother to infant. Antiretroviral regimens covering the later part of gestation, labour and the first few weeks of neonatal life have shown great efficacy in reducing such transmission. With the advent of combination antiretroviral therapies, transmission rates lower than 2% have been achieved in clinical studies. Elective caesarean delivery has been shown to enhance the benefit of antiretroviral regimens; however, the risks associated with this approach in many resource-poor settings in developing countries limit its role worldwide. Abbreviated antiretroviral regimens covering labour and the first few days of neonatal life have shown considerable promise in the developing world, resulting in 50% reduction in transmission.
BiapenemPerry, Caroline; Ibbotson, Tim
doi: 10.2165/00003495-200262150-00005pmid: 12381221
▴ Biapenem is a new parenteral carbapenem antibacterial agent with a broad spectrum of in vitro antibacterial activity encompassing many Gramnegative and Gram-positive aerobic and anaerobic bacteria, including species producing β-lactamases.
▴ Biapenem is more stable than imipenem, mero-penem and panipenem to hydrolysis by human renal dihydropeptidase-I (DHP-I), and therefore does not require the coadministration of a DHP-I inhibitor.
▴ After intravenous administration, biapenem is widely distributed and penetrates well into various tissues (e.g. lung tissue) and body fluids (e.g. sputum, pleural effusion, abdominal cavity fluid).
▴ In randomised, nonblind or double-blind clinical trials, biapenem showed good clinical and bacteriological efficacy (similar to that of imipenem/ cilastatin) in the treatment of adult patients with intra-abdominal infections, lower respiratory infections or complicated urinary tract infections.
▴ Biapenem is generally well tolerated. The most common adverse events in clinical trials were skin eruptions/rashes, nausea and diarrhoea.
GefitinibCuly, Christine; Faulds, Diana
doi: 10.2165/00003495-200262150-00008pmid: 12381224
▴ Gefitinib (ZD1839) is an orally active selective inhibitor of epidermal growth factor receptor tyrosine kinase, an enzyme that regulates intracellular signalling pathways implicated in the proliferation and survival of cancer cells.
▴ In human non-small cell lung cancer (NSCLC) cell lines and xenografts, gefitinib dose-dependently inhibited cellular proliferation and tumour growth, and potentiated the cytotoxic effects of chemotherapy and/or radiation.
▴ Gefitinib is orally bioavailable and is cleared via the cytochrome P450 3A4 pathway. In patients receiving gefitinib (50 to 700 mg/day) in phase I trials, steady-state plasma concentration was reached in 7 to 10 days.
▴ In patients with advanced NSCLC who had failed one or two prior chemotherapies, gefitinib 250 or 500mg once daily induced an objective response in ≈19% of patients in a double-blind trial (n = 210).
▴ In another double-blind trial including 216 patients with NSCLC who had failed two or more prior chemotherapies, gefitinib 250 or 500mg once daily induced an objective response in 11.8 and 8.8% of patients, respectively; ≈40% showed an improvement in disease-related symptoms.
▴ Gefitinib was generally well tolerated and the most common adverse events were mild skin rashes and diarrhoea.