Average daily dose

Note The RSD is an estimate of tlie average daily dose of a careinogen tliat... 

Oxicams, e.g. piroxicam, tenoxicam, meloxicam and lornoxicam are non-specific inhibitors of COX. Like diclofenac, meloxicam inhibits COX-2 ten times more potently than COX-1. This property can be exploited clinically with doses up to 7.5 mg per day, but at higher doses COX-1-inhibition becomes clinically relevant. Since the dose of meloxicam commonly used is 15 mg daily, this agent cannot be regarded as a COX-2-selective NS AID and considerable caution needs to be exercised when making comparisons between the actions of meloxicam and those of other conventional NSAIDs. The average daily dose in anti-rheumatic therapy is 20 mg for piroxicam and tenoxicam, 7.5-15 mg for meloxicam and 12-16 mg for lornoxicam. Oxicams have long elimination half-lives (lornoxicam 3-5 h, meloxicam - 20 h, piroxicam 40 h and tenoxicam 70 h). 

A total of 10,000 iterations or calculations of dose were performed as part of this simulation, and Figure 4 shows the resulting distribution of average daily doses of chlorpyrifos as determined by the Monte Carlo simulation. Common practice in exposure and risk assessment is to characterize the 50th percentile as a "typical" exposure and the 95th percentile as the "reasonable maximum" exposure.4 The distributional analysis for these calculated doses... 

Forecast Average Daily Dose Frequency Distribution... 

Figure 4 Monte Carlo simulation distribution of average daily dose.

Table 5 Average Daily Dose of Chlorpyrifos Estimated from Monte Carlo Simulation for Greenhouse Worker...

Stuer et al. [46] evaluated the presence of the 25 most used pharmaceuticals in the primary health sector in Denmark (e.g., paracetamol, acetyl salicylic acid, diazepam, and ibuprofen). They compared PECs with experimental determinations and they conclude that measured concentrations were in general within a factor of 2-5 of PECs. Carballa et al. [45] also determined PECs for pharmaceuticals (17), musk fragrances (2) and hormones (2) in sewage sludge matrix. For that purpose they used three different approaches (1) extrapolation of the per capita use in Europe to the number of Spanish inhabitants for musk fragrances (2) annual prescription items multiplied by the average daily dose for pharmaceuticals and (3) excretion rates of different groups of population for hormones. They indicated that these PECs fitted with the measured values for half of them (carbamazepine, diazepam, ibuprofen, naproxen, diclofenac, sulfamethoxazole, roxithromycin, erythromycin, and 17a-ethiny I e strad iol). 

In a case-control study (van Leeuwen et al. 1994) in which 98 cases of invasive endometrial carcinoma were diagnosed at least 3 months after diagnosis of primary breast cancer, it was observed that the use of tamoxifen was associated with a RR of 1.3. The risk appeared to have a tendency to increase during treatment, from 0.6 for less than a year to 3.0 for more than 5 years of treatment. It should be noted that the accumulated dose of tamoxifen was significantly associated with risk of endometrial cancer. However, the average daily dose used (20-40 mg/d) did not seem to influence risk. Other authors have also observed that the increase in risk is only detected when a determined accumulated dose is attained (van Leeuwen et al. 1994 De Muylder et al. 1991). 

Exposure Levels in Humans. The database for -hexane exposure levels in humans is limited to a few older detections of -hexane in breast milk and determinations of levels in body fluids and alveolar air collected in foreign countries. A more current and complete database would be helpful in determining the current exposure levels, thereby permitting the estimation of the average daily dose associated with various scenarios (e.g., living near a hazardous waste site). Since -hexane is rapidly metabolized within the human body, further studies correlating levels in the environment with the levels of metabolites and biomarkers in humans would be helpful. This information is necessary for assessing the need to conduct health studies on these populations. 

The general population can be exposed to chemical substances in indoor as well as in outdoor (ambient) air via inhalation of vapors, aerosols, and dusts in the air. The term inhalation exposure is defined as the concentration of a substance in inhaled air at the boundary of the body, and is expressed as an average concentration per unit time (e.g., mg/m per day). In order to estimate a daily dose of a substance from the exposure concentration of the substance in the air, the inhalation rate is used. According to US-EPA (1997), the average daily dose (ADD) can be estimated from the exposure concentration by using the following equation ... 

The ADD is the dose rate averaged over a pathway-specific period of exposure expressed as a daily dose on a per-unit-body-weight basis (US-EPA 1997). The ADD is used for exposure to chemicals with noncarcinogenic or nonchronic effects. Eor compounds with carcinogenic or chronic effects, the lifetime average daily dose (LADD) is used. The LADD is the dose rate averaged over a lifetime. The C refers to the concentration of the contaminant in inhaled air. The ED refers to the total time an individual is exposed to an air pollutant. 

In order to compare (no) effect levels across studies within a species, or across studies in different species it is often necessary to estimate the average daily dose to which the animals have been exposed. In order to estimate the average daily dose, expressed as mg/kg body weight per day. 

Because of the small number of patients studied in detail, no valid conclusions could be drawn about the precise limits of plasma chlorpromazine concentration for optimum therapeutic effect. Nevertheless, failure to respond to chlorpromazine was shown in one patient to relate to the extremely low plasma concentrations achieved—even by larger than average daily doses of chlorpromazine—whereas in another patient symptoms were aggravated when plasma levels of chlorpromazine were high. 

Hypertension PO Initially, 2.5 mg ql2h for 2 days, then increase by 2.5-mg increments at more than 2-day intervals until desired blood pressure is achieved. The average daily dose is 25 mg in 3 divided doses. 

The largest juvenile, controlled trial of a TCA reported favorable results with DMI in 62 clinically referred children with ADHD (Biederman et al., 1989). Many of these children had previously failed to respond to psychostimulant treatment. Sixty-eight percent of DMI-treated patients were considered very much or much improved, compared with only 10% of placebo patients (p < 0.001), at an average daily dose of 5 mg/kg. In a further analysis, neither comorbidity with conduct disorder, depression, or anxiety, nor a family history of ADHD yielded differential responses to DMI treatment (Biederman et al., 1993b). In addition, DMI-treated ADHD patients showed a substantial reduction in depressive symptoms compared with placebo-treated patients. 

This tricyclic drug is superior to placebo and equivalent to standard HCAs in outpatient populations. It is a more potent agent on a per milligram basis (i.e., average daily dose is 20 to 60 mg), partly because of its low first-pass effect and long half-life ( Table 7-5). Flence, patients develop substantially higher plasma levels per milligram dose of protriptyline versus other TCAs. 

---