Intravenous bolus plasma concentration

Fig. 22 (A) Plasma concentration of SMA-NCS and NCS in human after an intravenous bolus injection. (B) Intratumor concentration of SMA-NCS, NCS, and mitomycin (MMC). SMA-NCS exhibits a much higher and more prolonged tumor concentration than MMC and NCS. All drugs were given as an intravenous bolus at 10 mg/kg to rabbits bearing VX-2 tumor in...

The plasma concentration of a drug immediately following a 50-mg intravenous bolus dose of the drug was found to be 0.84 mcg/mL. What is the apparent volume of distribution of the drug ... 

The most sensitive technique for measuring brain uptake is the intravenous bolus administration or infusion and subsequent measurement of brain concentrations (Figure 2.4). Depending on the pharmacokinetics of the test compound in plasma, brain sampling may be performed after suitable circulation times ranging from minutes to hours or days. 

Laying-hens eliminate sulfadimidine rapidly by metabolic pathways including hydroxylation and acetylation. Following intravenous SDM administration, a biphasic elimination-time curve was noticed 10.2 + 3.3 H). Figure 8 shows the plasma disposition of SDM and its metabolites following an oral SDM bolus administration once daily of 100 mg/kg to a chicken. The percentage of N -SDM in plasma is the highest (Table I). Within 3 days of termination of the SDM therapy, plasma concentrations of SDM and its metabolites falls rapidly below the detection limit of the HPLC method (0.02 /ig/ml). 

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. 

Theoretical depiction of plasma concentrations following either an intravenous bolus dose immediately followed by initiation of a continuous intravenous infusion or initiation of a continuous intravenous infusion only. 

The changes in plasma and effect site concentrations following an intravenous bolus of propofol is shown in Figure 2.13. If the plasma concentration of a drug were instantaneously increased to a higher steady state concentration. 

Figure 2.13 The relationship between plasma (Cp) and effect site concentrations (Ce) following a single intravenous bolus of a drug.

Suppose an intravenous bolus is given at t = 0 and the drug concentration in the plasma is observed beginning at a time point t > 0. In Table 5.3 we list a data set of Cutler (ref. 20) generated by adding 1 /. relative errors of random character to the values of the weighting function... 

After intravenous administration of 175 mg/70 kg to five individuals, the average peak serum concentration was 1.0 mg/L achieved at 12 min.2 The concentration declined by 50% within 30 min. The plasma half-life is reported to be 3 to 4 h with a volume of distribution of 3 to 5 L/kg.1 Continuous infusion of 41 pg/kg/min after a 2-mg/kg bolus produced an average (n = 31) steady-state plasma concentration of 2.2 mg/L.3... 

Linear pharmacokinetics. For a simple linear pharmacokinetics case, the body can be modeled as a single drug compartment with first-order kinetic elimination—where the dose is administered and drug concentrations are drawn from the same compartment. For an intravenous bolus dose, the expected drug plasma concentration Cp versus time curves are shown in Fig. 1.10. The kinetics for this system are described by Eq. (1.6). The well-known solution to this equation is given by Eq. (1.7), and a linearized version of this solution is given in Eq. (1.8) and shown graphically in Fig. 1.13. 

A synthetic form of the endogenous peptide brain natriuretic peptide (BNP) has recently been approved for use in acute cardiac failure as nesiritide. This recombinant product increases cGMP in smooth muscle cells and effectively reduces venous and arteriolar tone in experimental preparations. It also causes diuresis. The peptide has a short half-life of about 18 minutes and is administered as a bolus intravenous dose followed by continuous infusion. Excessive hypotension is the most common adverse effect. Measurement of endogenous BNP has been proposed as a diagnostic test because plasma concentrations rise in most patients with heart failure. 

Plasma concentration profiles after buccal administration of the saturated drug solution varied considerably between animals but the overall time dependency was similar (Figure 4). Plasma levels increased rapidly after application of the solution onto the mucosa to produce relatively constant concentrations in the range 1500-8000 ng/ml after 2 h. Following removal of the solution the drug exhibited the expected decline in plasma concentrations at a rate comparable to that observed in the intravenous bolus study. 

After a bolus intravenous injection of 2 mg/kg followed by continuous intravenous infusion to provide a maintenance dose of 2 mg/kg to 1 neonate, plasma concentrations attained a steady-state of 7 to 8 pg/ml and declined with a half-life of 5 hours at the end of the infusion (V. Rovei et al., J. Chromat., 1982,231 Biomed. Appl., 20, 210-215). 

Figure 1 Plasma concentration time profiles for a single 42-mg dose of a hypothetical drug with a half-life of 8 hours, Vj 42 liters, and oral bioavailability of 80%. Dashed curve intravenous bolus dose. Solid curve oral dose. Dotted horizontal lines represent plasma concentrations required for efficacy (green) and for the onset of adverse events (red).

FIGURE 10.1 Fit obtained using a one-compartment model (see Equation 10.6) to fit plasma concentration-vs-time data observed following intravenous bolus administration of a drug designates the actual measured concentrations and Cp-g represents the concentrations predicted by the pharmacokinetic model. (Adapted from Grasela XH Jr, Sheiner LB. J Pliarmacokinet Biopharm 1991 19(suppl) 25S-36S.)... 

FIGURE 10.2 Fit obtained using a one-compartment model to fit plasma concentration-vs-time data observed following intravenous bolus administration of a drug. Each panel represents an individual patient. 

Figure 30.6 shows a prediction of the plasma concentration of ARA-C and total radioactivity (ARA-C plus ARA-U) following administration of two separate bolus intravenous injections of 1.2 mg/kg to a 70-kg woman. All compartment sizes and blood flow rates were estimated a -priori, and all enzyme kinetic parameters were determined from published in vitro studies. None of the parameters was selected specifically for this patient only the dose per body weight was used in the simulation. The prediction has the correct general shape and magnitude. It can be made quantitative by relatively minor changes in model parameters with no requirement to adjust the parameters describing metabolism. 

Aprotinin is not effective after oral administration, but is administered intravenously as a loading dose followed by a continuous infusion. Its activity is expressed as kallikrein inactivation units (KIU). The conventional (Munich) dose regimen consists of an initial 2 x 10 KIU bolus, a similar initial dose to prime the bypass machine, and then 0.5 x 10 KIU/ hour by continuous infusion thereafter. The half-life of aprotinin is about 2 hours. Plasma concentrations of 125 KlU/ml are necessary to inhibit plasmin, but a... 

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