After 50 years of clinical experience with the @entity4028 agents, there is continuing debate over the most appropriate administration regimen for these drugs. In recent years, once daily administration has been used increasingly, in the hope of both improving efficacy and reducing @entity137 . At least 30 controlled clinical trials have compared once versus conventional multiple daily administration. Efficacy was assessed in some, but not all, studies using clinical and/or bacteriological cure. @entity137 was generally determined using rather nonsensitive end-points such as measurement of serum @entity1011 for nephrotoxicity and clinically detectable @entity393 for @entity2167 . The results of individual clinical trials and subsequent meta-analyses have been variable. However, 5 of 9 meta-analyses found clinical efficacy to be significantly better with once daily administration, and in 3 of the 9 there were significantly less nephrotoxicity with once daily administration. The results were not significant for @entity2167 in any of the meta-analyses. There is debate about how therapeutic drug monitoring should be performed, and whether it is still required with once daily administration. Previous experience with the @entity581 , especially in @entity1 with impaired drug clearance caused by @entity8 , suggests that monitoring is still prudent. Results from the once daily administration trials appear to support this. Various methods of monitoring and dose adjustment have been proposed. The most common is to measure a 24-hour trough concentration and to adjust the dose to maintain the trough concentration below a value of 2, 1 or 0.5 mg/L. However, this method allows for greater total @entity4028 exposure than has been permitted with conventional dosages, increasing the likelihood of @entity137 in @entity1 with impaired @entity4028 clearance. Other methods measure drug concentrations at a time-point or points within the dose interval (when the concentration is still measurable), and adjust the dose according to concentration-time curve nomograms or to a target area under the concentration-time curve. This allows the use of higher doses in those with high drug clearance. Furthermore, in @entity1 with impaired clearance, drug exposure is limited to the same extent as, or less than, that with conventional multiple daily administration. To date no controlled trials have compared methods of dose-individualisation. In summary, in addition to a slight overall improvement in efficacy, once daily administration has resulted in a small reduction in nephrotoxicity. In the studies using more sensitive measures of @entity137 , the differences in @entity137 were greater, strengthening the case for once daily administration. Therapeutic drug monitoring is probably required with once daily administration. Methods which use mid-dosage interval concentrations to gauge drug exposure would seem to be preferable over trough concentration measurement.

Once daily XXXX therapy. Is it less toxic than multiple daily doses and how should it be monitored?

@entity1 :: ('9606', 'Species') :: ['patients'] @entity8 :: ('MESH:D007674', 'Disease') :: ['renal impairment'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'Toxicity'] @entity2167 :: ('MESH:D006311', 'Disease') :: ['ototoxicity'] @entity581 :: ('MESH:D000617', 'Chemical') :: ['aminoglycosides'] @entity1011 :: ('MESH:D003404', 'Chemical') :: ['creatinine'] @entity393 :: ('MESH:D034381', 'Disease') :: ['hearing loss'] @entity4028 :: ('CHEBI:47779', 'Chemical') :: ['aminoglycoside']
@entity4028 :: (CHEBI:47779,Chemical) :: ['aminoglycoside']
