Infusion duration concentration

Similar to that of cytarabine, conversion of gemcitabine to dFdCMP by deoxycytidine kinase is saturated at infusion rates of approximately 10 mg/m per minute, which produce plasma drug concentrations in the range of 15 to 20 pM. In an attempt to increase dFdCTP formation, the duration of infusion at this maximum concentration has been extended to 150 minutes. In contrast to a fixed infusion duration of 30 minutes, the 150-minute infusion produces a higher level of dFdCTP within peripheral blood mononuclear cells and increases the degree of myelosuppression, but has uncertain effects on antitumor activity. 

This should be compared with the initial plasma concentration of 50 pg F which is obtained when the same dose D is injected as a single bolus. The final concentration Cp(x) is also still far from the steady-state concentration (72.2 pg 1" ), since the duration of infusion x is only equal to once the half-life time of the dmg t,/2 (60 min). 

Absorption/Distribution - Lidocaine is ineffective orally it is most commonly administered IV with an immediate onset (within minutes) and brief duration (10 to 20 minutes) of action following a bolus dose. Continuous IV infusion of lidocaine (1 to 4 mg/min) is necessary to maintain antiarrhythmic effects. Following IM administration, therapeutic serum levels are achieved in 5 to 15 minutes and may persist for up to 2 hours. Higher and more rapid serum levels are achieved by injection into the deltoid muscle. Therapeutic serum levels are 1.5 to 6 mcg/mL serum levels greater than 6 to 10 mcg/mL are usually toxic. Lidocaine is approximately 50% protein bound (concentration-dependent). 

Figure 2.7 Decline in the plasma concentration following cessation of intravenous infusions of different durations. The plasma concentrations at termination of the infusion have been normalised to 100.

Extent and duration of action of various types of insulin as indicated by the glucose infusion rates (mg/kg/min) required to maintain a constant glucose concentration. The durations of action shown are typical of an average dose of 0.2-0.3 U/kg. The durations of regular and NPH insulin increase considerably when... 

The clinically recommended dose of bivalirudin was originally 1.0 mg/kg bolus followed by infusion at 2.5 mg/kg/hr for four hours. After the REPLACE-2 trial, the dose was reduced to 0.75 mg/kg bolus followed by an infusion of 1.75 mg/kg/hr for the duration of the PCI procedure, which is the dosage approved in the United States and Europe. The postprocedural infusion can be continued for up to four hours. It is recommended that ACT should be measured five minutes after bolus dosing, where ACT is expected to be 320 to 400 seconds, and a second bolus of 0.3 mg/kg should be administered if needed [if ACT is less than 225 seconds according to the EMEA Sm PC (68)]. Bivalirudin shows a linear correlation between the dose or plasma concentration and... 

In practice, it is unlikely to have compartmental models with initial conditions unless there are residual concentrations obtained from previous administrations. Drugs are administered either by extravascular, or intravascular in single or repeated experiments. Extravascular routes are oral, or intramuscular routes, and intravascular are the constant-rate short- and long-duration infusions. 

Since there is a direct link between the Effect and plasma concentration, such PK/PD model could be used for generating duration of effect curves after either bolus dosing, infusion or a combination of bolus plus infusion. To do this, the plasma concentrations from the PK profile were used as input values to arrive at the corresponding Effect values such that in the end, one would have a Effect versus Time profile. For... 

The safety and efficacy of low dose ABLC (1 mg/kg/day) for empirical treatment of fever and nentropenia have been studied in 69 episodes in 61 patients with hematological malignancies (35). The median duration of therapy was 8 (range 2-19) days and 13 patients had mUd to moderate infusion-related adverse events. Creatinine concentrations remained stable in 42 cases, improved in 9, and deteriorated in 18. There were no other toxic effects. The response rate (resolution of fever dnring neutropenia and absence of invasive fungal infection) was 67%. 

Fluid retention has previously been reported with docetaxel. Some believe that this effect depends on the dose and the duration of infusion (3,4) and that high concentrations of M4, the cyclized oxazolidinedione metabolite of docetaxel, cause more pronounced fluid retention. 

The clinical significance of antibodies to infliximab has also been explored in 125 patients with Crohn s disease who were given infliximab, of whom 61% had antibodies after the fifth infusion however, there was no further increase in incidence after subsequent treatment (21). The presence of antibodies was associated with a 2.4-fold increase in the risk of infusion reactions, lower serum infliximab concentrations, and a shorter duration of clinical response, compared with patients with no infliximab antibodies. Patients who received concomitant immunosuppressive therapy had a lower incidence of infliximab antibodies, higher infliximab serum concentrations, and a longer duration of clinical response. Pretreatment with glucocorticoids may reduce the risk of antibody formation, but it is not known whether a pretreatment test for human antichimeric antibodies has a predictive value for adverse reactions (22). However, there were technical issues relating to the antibody assay and definition of clinically relevant antibody titers in this study. 

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