Dose interval

Plasma dmg concentrations rise at a gradual, controlled rate after dosing, and reach a plateau at approximately 6 h after the first dose with minimal fluctuations over the 24 h dosing interval. Subsequent doses maintain the plasma concentration at this plateau. The extended release tablets taken once daily have reduced by fourfold the fluctuations (ratio of peak to trough plasma concentration) observed with the conventional immediate release Procardia tablets taken three times daily (81). 

COMT inhibitors rescue l-dopa and improve the brain entry of L-dopa by decreasing 3-OMD formation in peripheral tissues. The dose of L-dopa could be decreased, compared with the present combination therapy. Dose interval of L-dopa could also be prolonged. Further, COMT inhibitors should decrease fluctuations of dopamine formation in the brain. 

Locomotion, stereotypy, and ataxia were rated via behavioral observations for all compounds, using behavioral rating scales devised specifically for PCP (Sturgeon et al. 1979). Behaviors were rated by observing each animal for 1 or 2 minutes at the midpoint of each 30-minute dosing interval during collection of the EEG. 

Antibiotic Pediatric Dose (mg/kg per day) Adult Maximum Daily Dose Interval (Hours)... 

In patients with fistulae, monitor at every infliximab dosing interval for evidence of fistula closure and overall reduction in the number of fistulae. 

Opioids maybe administered in a variety of routes including oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, intravenous, subcutaneous, and intraspinal. While the oral and transdermal routes are most common, the method of administration is based on patient needs (severity of pain) and characteristics (swallowing difficulty and preference). Oral opioids have an onset of effect of 45 minutes, so intravenous or subcutaneous administration maybe preferred if more rapid relief is desired. Intramuscular injections are not recommended because of pain at the injection site and wide fluctuations in drug absorption and peak plasma concentrations achieved. More invasive routes of administration such as PCA and intraspinal (epidural and intrathecal) are primarily used postoperatively, but may also be used in refractory chronic pain situations. PCA delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Morphine, fentanyl, and hydromorphone are commonly administered via PCA pumps by the intravenous route, but less frequently by the subcutaneous or epidural route. 

Use of the first-generation somatostatin analog octreotide is limited by its extremely short duration of action and requirement for subcutaneous administration at least three times a day. If a patient s GH level returns to baseline before the end of an 8-hour dosing interval, the frequency of octreotide administration can be increased to every 4 to 6 hours. Most patients require octreotide in doses of 100 to 200 meg three times daily.19,20 To improve patient tolerance to gastrointestinal (GI) adverse effects, start octreotide at 50 meg every 8 hours.20 Assess IGF-I serum concentrations every 2 weeks after initiating therapy to further titrate dose in increments of 50 meg per dose. 

Dose Increments (mg) Dose Interval Cumulative Dose (mg)... 

Provide patient education with regard to appropriate use of antimicrobials (e.g., dose, interval), adverse effects, and drug interactions (which may play a role in therapy failure and increased toxicity). 

Because they are hepatically cleared, isoniazid and rifampin do not require dose modification in renal failure.31,36,39 Pyrazinamide and ethambutol typically are reduced to three times weekly to avoid accumulation of the parent drug (ethambutol) or metabolites (pyrazinamide).28,31 Renally cleared TB drugs include the aminoglycosides (e.g., amikacin, kanamycin, and streptomycin), capreomycin, ethambutol, cycloserine, and lev-ofloxacin.28,31,33,39 Dosing intervals need to be extended for... 

The plasma concentrations in Fig. 14 can be calculated as follows from Eq. (25) the plasma concentration at the end of the first dosing interval, T, is given by ... 

It is now helpful to define the parameter R as the fraction of the initial plasma concentration that remains at the end of any dosing interval R is given by the following equation ... 

As was pointed out in Sec. VI, when T = t /2, R = 0.5. The plot in Fig. 14 was constructed using these conditions therefore, the plasma concentration at the end of each dosing interval is half the concentration at the beginning of the dosing interval. 

The plasma concentrations at the beginning and end of the nth dosing interval are given by the following power series ... 

The maintenance dose needed to replace the amount lost over the dosing interval is the difference between the loading dose and the amount remaining at the end of the interval ... 

The time units for the dosing interval (7) and the step interval (int) must be the same as those for the half-lives of elimination and absorption. 

Once the number of maintenance doses (n) is entered the spreadsheet calculates Cp for the nth dosing interval. 

Infants and children older than 1 year of age are considered to be very efficient metabolizers of drugs and may actually require larger doses than those predicted by weight adjustment of adult doses or shorter dosing intervals [33], On the basis of metabolic activity, sustained-release formulations would appear to be ideal for children 1-10 years old, if bioavailability issues prove not to be problematic. The ability to clear drugs in critically ill children may be severely compromised therefore, dosing in this subgroup of patients requires careful titration [34]. 

Even the most superficial evaluation of bioequivalency requirements for controlled-release products will indicate that for some of these products, at least, the conventional AUC, Tmax, and Cmax measures of bioequivalency may well be insufficient. Thus, for a non-pulsatile sustained-release product with a dosing interval of 24 hours (as compared to 4 hours for the noncontrolled product), the time period during which plasma concentrations are maintained at essentially a plateau level might well be regarded as of critical... 

All these aspects of tight binding inhibition can potentially offer important advantages in terms of clinical efficacy, dosing interval, and patient safety (see Swinney, 2004, for an excellent review of some of the clinical advantages of tight binding inhibition and other nonclassical inhibition mechanisms). 

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