Therapeutic concentration range

There is no standard definition of intravitreal injection toxicity. Histopathologic criteria are most frequently used in animal models. Various authors evaluate changes 

Electroretinographic toxicity criteria have also been employed but concurrent controls in which a placebo is injected in the fellow eye simultaneously are important since surgical invasion of the eye alone can reduce the electroretinographic response (33). The antimicrobial itself, the vehicle, or the preservatives may all be sources of intraocular toxicity. Osmolality or pH have been suggested by Marmor as potential causes for iatrogenic tissue damage to the retina (34). Injection of low volumes of drug probably minimizes this risk. 

Peyman et al. (35) hypothesized that the injection of antibiotic into an eye from which vitreous has been removed might increase the risk of toxicity. Lim demonstrated that the settling of aminoglycosides onto the retinal surface in vitrectomized eye did in fact predispose the eyes to higher local doses on the retinal surface and therefore to higher risk of toxicity (27). 

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By contrast, in the population approach, the raw data set that is analysed consists of concentration-time points (and other necessary data such as demographic information) taken from a large number (up to hundreds to thousands) of patients in Phase 11 and/or Phase 111 trials. The number of plasma samples per subject may be sparse but it is possible to estimate the individual pharmacokinetic characteristics of each subject and hence a measure of the mean parameters and their variability can be assessed. Relationships can be sought between patient characteristics (demographics, chnical status) and pharmacokinetic values is found, its consequence may be examined by looking for altered efficacy or safety which may not be possible in a traditional volunteer study. This might lead to demonstration of a therapeutic concentration range. 

Any significant changes in process or product formulation may also have significant impact on pharmacology, affecting therapeutic concentration range or window, bioavailability, or therapeutic... 

At present the plastic membrane with ionophore ETH 2137 is used. The introduction of ionophore ETH 2137 generated a stable selectivity towards sodium ion allowing for numerical correction of sodium influence using the values of independently measured sodium. Thus a complete procedure covering therapeutic concentration range of lithium (which should be <1.2mmol/L) is available. 

Because theophylline has a relatively narrow therapeutic index, it would be desirable to determine a dose at which the maximal and minimal concentrations at steady state will be within the therapeutic concentration range (5-15mg/L). Therefore, the 280 mg bid dose regimen is convenient and adequate to achieve Cmax and Cmin within the therapeutic range. 

The overall goal in designing sustained relea.se oral dosage forms is to provide systemic drug concentrations that remain within the therapeutic concentration range for a... 

Renal disease (uraemia) may increase the volume of distribution of acidic drugs that extensively bind to plasma albumin (e.g., phenytoin, valproic acid, naproxen, phenylbutazone, furosemide). As decreased protein binding would increase the unbound (free) fraction in the plasma, the therapeutic concentration range (based on total drug concentration) would be lower than the usual... 

The therapeutic concentration range for optimal pharmacological effect of carbamazepine is 4 to 12p,g/mL. Toxicity associated with excessive carbamazepine ingestion occurs at plasma concentrations in excess of 15p.g/mL and is characterized by symptoms of blurred vision, paresthesia, nystagmus, ataxia, drowsiness, and diplopia. Side effects unrelated to plasma concentration include development of an urticarial rash, which usually disappears on discontinuation of the drug, and hematological depression (leukopenia, thrombocytopenia, and aplastic anemia). 

The therapeutic concentration range can be defined, particularly if therapeutic drug monitoring is likely to be useful because of a narrow therapeutic index and/or a clear concentration-effect relationship. 

A. Specific levels. Serum phenytoin concentrations are generally available in all hospital clinical laboratories. Obtain repeated blood samples because slow absorption may result in delayed peak levels. The therapeutic concentration range is 10-20 mg/L. 

The in vitro plasma protein binding has been reported to be stereoselective for many NSAIDs such as ibuprofen, flurbiprofen, ketoprofen, and etodolac (Table 3) [261-265]. Ibuprofen protein binding is stereoselective and nonlinear within the therapeutic concentration range (1 to 50mg/L) [259]. The S enantiomer reportedly has a higher unbound fraction than antipode in human plasma [261,266]. An apparent decrease in the... 

Chromatographic (LC—MS) and solid-phase extraction (SPE) conditions have been optimized for Clozapine, with cycle times of 2.2 min. Depending on the ionization modes detection hmits varied between 0.15 and 0.3 mg/ml. A quadratic calibration curve was found for clozapine and its N-oxide and a linear one for the desmethyl metabohte (R > 0.99 in all cases). Accuracy is better than 10% in the whole therapeutic concentration range. Interassay precision 5-20% of the standard deviation from the highest to the lowest therapeutic concentrations. Quantitative measurements are possible down to 350 ng/ml. 

A 1-ml portion of plasma was extracted twice (pH 7.4 and 12] using a 1 1 mbcture of diethyl ether and ethyl acetate after addition of methaqualone as internal standard. The extract was analyzed by GC-MS in the selective-ion monitoring (SIM) mode (m/z 185, 187, 255, 257 for lamotrigine and 235, 250 for methaqualone). A five-point calibration graph was established using spiked plasma samples [65]. The procedure was linear from 0.5 to 20 mg/L (r = 0.991) with coefficients of variation of less than 15%. The LOD was 0.1 mg/L. As we have seen, therapeutic concentrations ranged from 1 to 6 mg/L. The presented method has proved to be suitable for TDM as well as for clinical toxicology. 

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