Plasma steady-state plasmas

The molecules that are dissociated and the atoms that are ionized during plasma production can be in any state at the start. Steady-state plasmas are formed most often from gases, although Hquids, such as volatile organics, and soHds are also used. Gases and soHds routinely serve as sources of material in pulsed plasma work. 

Elecainide is weU absorbed and 90% of the po dose is bioavailable. Binding to plasma protein is only 40% and peak plasma concentrations are attained in about 1—6 h. Three to five days may be requited to attain steady-state plasma concentrations when multiple doses are used. Therapeutic plasma concentrations are 0.2—1.0 lg/mL. Elecainide has an elimination half-life of 12—27 h, allowing twice a day dosing. The plasma half-life is increased in patients with renal failure or low cardiac outputs. About 70% of the flecainide in plasma is metabolized by the Hver to two principal metaboUtes. The antiarrhythmic potency of the meta-O-dealkylated metaboUte and the meta-O-dealkylated lactam, relative to that of flecainide is 50 and 10%, respectively. The plasma concentrations of the two metaboUtes relative to that of flecainide are 3—25%. Elecainide is mainly excreted by the kidneys, 30% unchanged, the rest as metaboUtes or conjugates about 5% is excreted in the feces (1,2). 

AUC is the area under the curve or the integral of the plasma levels from zero to infinite time. Conversely, equation 1 may be used to calculate input rates of dmg that would produce steady-state plasma levels that correspond to the occurrence of minor or major side effects of the dmg. 

Theoretical volume of distribution (Vj) of a chemical is the volume in which the chemical would be distributed if its concentration were equal to a theoretical steady-state plasma concentration (Cq) at time zero. The volume of distribution is thus obtained quite similarly as the steady state concentration of a compound in the workroom air ... 

FIGURE 8.25 Repeated oral administration of drags leads to steady-state plasma concentrations. If elimination is rapid and administration not often enough, then an elevated and therapeutically effective steady-state concentration may not be achieved (green lines). In contrast, if elimination is very slow (or administration too often), then an accumulation of the drag may be observed with no constant steady state (red line). Bine line shows a correct balance between frequency of administration and elimination. 

Ciraulo DA, Sands BE, Shader RI Critical review of liability for benzodiazepine abuse among alcoholics. Am J Psychiatry 145 1501-1506, 1988b Ciraulo DA, Barnhill JG, Ciraulo AM, et al Parental alcoholism as a risk factor in benzodiazepine abuse a pilot smdy. Am J Psychiatry 146 1333-1335, 1989 Ciraulo DA, Antal EJ, Smith RB, et al The relationship of alprazolam dose to steady-state plasma concentrations. J Clin Psychopharmacol 10 27—32, 1990 Ciraulo DA, Sarid-Segal O, Knapp C, et al Liability to alprazolam abuse in daughters of alcoholics. Am J Psychiatry 153 956-958, 1996 Ciraulo DA, Barnhill JG, Ciraulo AM, et al Alterations in pharmacodynamics of anxiolytics in abstinent alcoholic men subjective responses, abuse liability, and electroencephalographic effects of alprazolam, diazepam, and buspirone. J Clin Pharmacol 37 64-73, 1997... 

In humans, peak plasma or serum concentrations of lutein occurred 11 to 16 hr after administration of a single oral dose. During daily supplementation with 20 mg of lutein, steady-state plasma concentrations were reached in about 30 days. This is consistent with an elimination half-life of 5 to 7 days. 

If the infusion is maintained for a sufficiently long time x, one obtains the condition for a steady-state plasma concentration which no longer changes with time. The condition follows immediately from eq. (39.34), by setting rto infinity ... 

Note that the steady-state plasma concentration varies proportionally with the rate of infusion and inversely with the plasma clearance C/p, the definition of... 

In practice, one will seek to obtain an estimate of the elimination constant kp and the plasma volume of distribution Vp by means of a single intravenous injection. These pharmacokinetic parameters are then used in the determination of the required dose D in the reservoir and the input rate constant k (i.e. the drip rate or the pump flow) in order to obtain an optimal steady state plasma concentration... 

In this special case when the time between dosings is equal to the half-life time of the drug, we can deduce that the minimum (steady-state) plasma concentration with repeated dosing is equal to the peak concentration, obtained from a single dose. Under this condition, the corresponding maximum (steady-state) concentration is twice as much as the minimum one. 

From the above solution we can now easily determine the steady-state plasma content X after a sufficiently long time t ... 

A recent study compared the differences in dosage and steady state plasma concentrations of sertraline, in Chinese versus Caucasian depressed outpatients. 

Several cases of sudden death have been reported in children and adolescents taking desipramine. A baseline electrocardiogram (ECG) is recommended before initiating a TCA in children and adolescents, and an additional ECG is advised when steady-state plasma concentrations are achieved. TCA plasma concentration monitoring is critical to ensure safety. 

By simultaneous monitoring of tidal volume and respiratory rate, or minute volume, and the concentration of an inhaled vapor in the bloodstream and the vapor in the exposure atmosphere, pharmacokinetic studies on the C t relationship have shown that the effective dose was nearly proportional to the exposure concentration for vapors such as 1,1,1-trichloroethane (Dallas et al., 1986), which has a saturable metabolism, found that the steady-state plasma concentrations were disproportion-ally greater at higher exposure concentrations. 

Ishida, M., Otani, K., Kaneko, S., Ohkubo, T., Osanai, T., Yasui, N., Mihara, K., Higuchi, H. and Sugawara, K. (1995) Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine. International Clinical Psychopharmacology, 10 (3), 143-146. 

PK Following an oral dose, plasma peak concentration is achieved in approximately 6 hours. About 40% is eliminated through first pass metabolism. The half-life is from 21 to 54 hours and plasma clearance is from 12 to 47 hours. Daily administration will lead to a steady-state plasma concentration in about a week with concentration twice that of the single dose. Metabolism of Zyprexa is by the cytochrome P-450 oxidation. 

Varsaldi, F., MigUo, G., Scordo, M.G., et al. (2006) Impact of the CYP2D6 polymorphism on steady-state plasma concentrations and clinical outcome of donepezil in Alzheimer s disease patients. Eur. J. Clin. Pharmacol., 62, 721-726. 

In calves and cows at high dose levels (100 SDM mg/kg), a biphasic elimination SDM plasma concentration-time curve was observed with a steady state plasma SCH2OH concentration resulting from the capacity limited hydroxylation of SDM into the latter. The drug concentrations in the milk reflected those in plasma. 

A steady plasma level can be achieved by giving the drug in a constant intravenous infusion, the steady-state plasma level being determined by the infusion rate, dose D per unit of time T, and the clearance, according to the equation n... 

That blood drug measurements can sometimes provide valuable additional information is, however, not seriously in doubt. For some drugs the intensity of the pharmacological action and severity of side-effects correlates much better with the plasma steady-state concentration than with... 

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