Time to reach maximum plasma concentration

Pharmacokinetics Disulfiram is slowly absorbed from the Gl tract and eliminated slowly from the body. The average time to reach maximum plasma concentrations... 

Mean Cmax and AUC(o 24) (= AUCX) both on day 1 (Cmax 0.46, 1.16 and 3.29 pg/mL AUCX 7.12, 16.37 and 39.85 pg h/mL) and on day 7 (Cmax,ss 0.91, 2.31 and 5.95 pg/rnL AUCX,SS 14.17, 33.55 and 74.48 pg h/mL) increased with increasing dose although the increases were marginally higher than strict dose proportionality would predict the deviation from linearity was however minor. The median time to reach maximum plasma concentration was 6 h on both profile days and at all doses. The terminal phase half-fife of XYZ1234 on day 7 was quite constant with mean values between 19 to 23 h a slight reduction in half-life (accompanied by a reduced terminal phase volume of distribution) was observed at the higher doses. 

After oral doses of 50-200 mg, sertraline reaches a maximum plasma concentration in 4.5-8.4h. Administration of the oral concentrate results in a higher area under the curve (AUC) and Cmax compared to the oral tablet. Peak absorption may be delayed with large ingestions. When food was administered with therapeutic doses of tablet formulation, both the peak and total plasma levels (AUC) increased however, the time to reach peak plasma concentration decreased. With repeated dosing, a steady-state plasma level should be achieved within 7 days. 

Overall no correlation was observed between dose and Tmax. However, hypericin took longer to reach maximum plasma concentration. This corresponds with the lag time data (41). 

Commercial samples containing approximately 400 mg of ephedra per capsule yield roughly 5 mg of ephedrine, 1 mg of pseudoephedrine, and less than 1 mg of methylephedrine (White et al. 1997). For a dose of four capsules, yielding approximately 20 mg of ephedrine, the elimination half-life is 5.2 hours. The time to reach maxium concentration is 3.9 hours. Compared to pure ephedrine tablets, the elimination kinetics of ephedra are comparable. However, ephedra showed somewhat different absorption kinetics (e.g., lag time, area under the concentration-time curve, and maximum plasma concentration). So, ephedra tablets may vary from pure ephedrine in the onset of action, but the durations of action are grossly equivalent. 

The persistence of flumequine residues in eel plasma and tissues was also determined for a 44 day period following a single intramuscular injection (168). The time to reach maximum concentrations of flumequine in tissues (48-192 h) was comparable to that in plasma (96 h). Mean maximum concentrations in tissues ranged from 725 ppb in bone to 121,000 ppb in fat. These concentrations declined with time in all tissues to reach, 44 days after administration, the values of 769, 427, 238, 213, 197, 153, 89, and 85 ppb in liver, fat, muscle, plasma, spleen, skin, bone, and kidney, respectively. 

Phencyclidine is typically self-administered by the oral, intravenous, or smoked routes. After oral administration to healthy human volunteers, the bioavailability was found to vary between 50 and 90%.4 In this study, peak plasma concentrations were achieved after 1.5 h and appeared to correlate with the time to reach maximum pharmacological effects. However, because there have been no comprehensive clinical controlled studies of phencyclidine, a correlation between PCP blood concentrations and pharmacological effects has not been definitively documented. Maximum serum PCP concentrations ranged between 2.7 and 2.9 ng/ml after 1 mg PCP administered orally.4... 

Saturable absorption Time to reach maximum PHT plasma concentrations after a single oral dose increases with the dose with doses >400 mg. ... 

For data presentation, tissue radioactivity levels are expressed as nanogram-equivalents per gram tissue (Table 18.Al), and tissue/plasma ratios. The maximum concentration (Cmax) and the time to reach maximum concentration (Fmax) are obtained by visual inspection of the raw data. Pharmacokinetic parameters, included half-life (fi/2), area under the concentration-time curve... 

These effects could result from the progression of the disease but as they are a feature of levodopa therapy a change in the central response to levodopa or changes in its peripheral kinetics are more likely. The latter does not occur since the maximum plasma concentration, the time to reach it and the plasma half-life are still similar after 10 years of treatment to those achieved initially, although continuous infusion of dopa can smooth out the swings. 

Absorption - Nalmefene is completely bioavailable following IM or subcutaneous administration. Nalmefene will be administered primarily as an IV bolus however, it can be given IM or subcutaneous if venous access cannot be established. While the time to maximum plasma concentration was 2.3 hours following IM and 1.5 hours following subcutaneous administrations, therapeutic plasma concentrations are likely to be reached within 5 to 15 minutes after a 1 mg dose in an emergency. 

Again we will take blood samples at intervals after dosing, measure plasma drug concentrations, and plot the results on a linear graph (Fig. 11). The first and obvious thing to note is that the plasma concentrations rise to a maximum at around 1 h, whereas, of course, the early plasma concentrations taken soon after the intravenous bolus were the highest. The time to reach the peak plasma concentration after an oral dose is often abbreviated to Tmax, and the concentration itself to Cmax - the maximum concentration achieved after that dose. 

Figure 30.27 Time to reach the maximum temperature during the polymerization of PMMA bone cement as a function of peroxide concentration on the plasma-treated X-ray opaque powder surfaces.

An indication of the rate of drug absorption can be obtained from the peak (maximum) plasma concentration (Cmax) and the time taken to reach the peak concentration (fmjx), based on the measured plasma concentration-time data. However, the blood sampling times determine how well the peak is defined and, in particular, fmax. Both Cmax and tm3LX may be influenced by the rate of drug elimination, while Cmax is also affected by the extent of absorption. The term Cmax/ AUC, where AUC is area under the curve from time zero to infinity or to the limit of quantification (LOQ) of the analytical method, provides additional information on the rate of absorption. This term, which is expressed in units of reciprocal time (h ), can easily be calculated. In spite of the imprecision of the estimation provided by Cmax, it generally suffices for clinical purposes. 

Pharmacokinetic Tools to Characterize Absorption Kinetics. The sustained character of lung absorption is important for the degree of pulmonary selectivity. It is therefore important to evaluate lung absorption with pharmacokinetic tools. Several tools have been used to provide this information, including the time to reach the maximum plasma concentration (tmax), the mean absorption time (MAT), flip-flop, and deconvolution. These approaches are described next. 

As far as the rate component of bioavailability is concerned, it is estimated by two parameters, Cmax and tmax. The maximum plasma concentration (Cmax) is related to (a) total plasma clearance (b) the fraction of dose that reaches the general circulation without being metabolized (c) the rate of absorption and (d) the rates of distribution and elimination. The time to reach Cmax (tmax) depends on (a) the rate of absorption and (b) the rates of distribution and elimination. 

GHB exhibits zero-order (constant rate) elimination kinetics after an intravenous dose. Since GHB exhibits zero-order kinetics, it has no true half-life. The time required to eliminate half of a given dose increases as the dose increases. A daily therapeutic dose of 25 mg kg has an apparent half-life of about 30 min in humans, as determined in alcohol dependent patients under GHB treatment (Ferrara et al., 1992). In contrast, an apparent half-life of 1-2 h was observed in dogs when they were given high intravenous doses of GHB. In humans it has been documented that there is increased rate of absorption if GHB is administered on an empty stomach, resulting in a reduced time to reach the maximum plasma concentration of GHB (Borgen et al., 2001). 

The standard bioavailability variables after a single-dose administration are the maximum plasma concentration (Cmax), the time to reach Cmax (fmax) and the area under the plasma concentration—time curve from time zero to infinity (AUC). 

Note C is the maximum plasma concentration is the time to reach the maximum plasma concentration AUG is the area under the plasma concentration-time curve Tjq is the elimination half-life absorption in plasma (%) is the percentage of the total dose of ingested tea catechins in plasma and excretion in urine (%) is the percentage of the total dose of ingested tea catechins excreted in urine. 

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