Peak concentration/levels

Medroxyprog esteroneAcetate. Accurate pharmacokinetic and metaboHsm studies on MPA have been difficult because the radioimmunoassays employed caimot differentiate between MPA and its metaboHtes (346). Comparison of MPA plasma levels assayed by hplc and radioimmunoassay show that radioimmunoassay may overestimate intact MPA concentrations by about fivefold (347). However, values of the mean elimination half-life of MPA were similar, being 33.8 and 39.7 h when measured by hplc and radioimmunoassay, respectively (347). Approximately 94% of MPA in the blood is bound to albumin (348). When taken orally, MPA is rapidly absorbed with Htde or no first-pass metaboHsm (13). Peak semm levels ate reached after 3 h. Steady state occurs after three days of daily adininistration (349). The pharmacokinetics of MPA when adininistered in a depot formulation have been described (350). 

Although the naturally occurring concentration of ozone at the earth s surface is low, the distribution has been altered by the emission of pollutants, primarily by automobiles but also from industrial sources which lead to the formation of ozone. The strategy for controlling ambient ozone concentrations arising from automobile exhaust emissions is based on the control of hydrocarbons, CO, and NO via catalytic converters. As a result, peak ozone levels in Los Angeles, for instance, have decreased from 0.58 ppm in 1970 to 0.33 ppm in 1990, despite a 66% increase in the number of vehicles. 

Methadone is a p receptor agonist with special properties that make it particularly useful as a maintenance agent. Rehably absorbed orally, it does not reach peak concentration until about 4 hours after administration and maintains a large extravascular reservoir (Kreek 1979). These properties minimize acute euphoric effects. The reservoir results in a plasma half-life of 1—2 days, so there are usually no rapid blood level drops that could lead to withdrawal syndromes between daily doses. Effective blood levels are in the range of 200-500 ng/mL. Trough levels of 400 ng/mL are considered optimal (Payte and Khouri 1993). There is wide variability among individuals in blood levels with identical doses (Kreek 1979), and some have inadequate levels even with doses as high as 200 mg/day (Tennant 1987 Tenore 2003). 

The distribution of endosulfan and endosulfan sulfate was evaluated in the brains of cats given a single intravenous injection of 3 mg/kg endosulfan (Khanna et al. 1979). Peak concentrations of endosulfan in the brain were found at the earliest time point examined (15 minutes after administration) and then decreased. When tissue levels were expressed per gram of tissue, little differential was observed in distribution among the brain areas studied. However, if endosulfan levels were expressed per gram of tissue lipid, higher initial levels were observed in the cerebral cortex and cerebellum than in the spinal cord and brainstem. Loss of endosulfan was most rapid from those areas low in Upid. Endosulfan sulfate levels peaked in the brain at 1 hour postadministration. In contrast, endosulfan sulfate levels in liver peaked within 15 minutes postadministration. The time course of neurotoxic effects observed in the animals in this study corresponded most closely with endosulfan levels in the central nervous system tissues examined. 

Experiments demonstrate that oral absorption of trichloroethylene in animals is extensive and metabolism is rapid. A study of F344 rats which were fasted for 8 hours prior to oral dosing by gavage found a rapid appearance of trichloroethylene in the blood which peaked after 0.75 hours, while the peak concentrations of the metabolites trichloroethanol and TCA occurred at 2.5 and 12 hours, respectively (Templin et al. 1995). The same investigators also dosed beagle dogs and found that blood concentrations of trichloroethylene, trichloroethanol, and TCA peaked after 1, 2.5, and 24 hours, respectively. In both species, TCA concentration did not peak until well after the trichloroethylene concentration in blood was below detectable levels (Templin et al. 1995). 

In the author s experience, such confirmation is not appropriate when the calibration range is greater than one order of magniffide or calibration points are not chosen carefully. The reason is that lower concentration levels of a calibration graph influence the correlation coefficient to a much smaller extent than higher concentrations. The hypothetical example of calibration results presented in Table 3 demonstrates this very simply. If the amount injected is correlated with the observed peak area in the second column in Table 3, the calibration graph in Figure 2 is obtained. 

Modifiers can be used very effectively in on-line SFE-GC to determine the concentration levels of the respective analytes. This presents an advantage in terms of the use of modifiers in SFE, since they appear as solvent peaks in GC separations and do not interfere with the target analyte determination. Although online SFE-GC is a simple technique, its applicability to real-life samples is limited compared to off-line SFE-GC. As a result, on-line SFE-GC requires suitable sample selection and appropriate setting of extraction conditions. If the goal is to determine the profile or matrix composition of a sample, it is required to use the fluid at the maximum solubility. For trace analysis it is best to choose a condition that separates the analytes from the matrix without interference. However, present SFE-GC techniques are not useful for samples... 

In animals, diisopropyl methylphosphonate absorbed from the gastrointestinal tract is rapidly distributed to the tissues as indicated by the decay in peak plasma levels after absorption (Hart 1976 Ivie 1980). In mice, plasma radioactivity declined slowly from 15 minutes to 1 hour after exposure and then dropped rapidly during the next 2 hours. At the end of 24 hours, the label in the blood was 0.63 g/mL or 0.3% of the 173- g/mL peak concentration (Hart 1976). The radiolabel in the plasma of rats after 24 hours was nearly identical to that in mice (0.61 g/L) and was 0.4% of the peak concentration. Clearance of label was slower in dogs with 1.3% of the 276- g/L peak concentration present after 24 hours. 

Table 2 Peak Plasma Levels and Areas Under Plasma Concentration Time Curves Following Oral and Intravenous Administration to Men...

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