Intravenous injection pharmacokinetics

Pharmacokinetics Intravenous injection of vincristine or vinblastine leads to rapid cytotoxic effects and cell destruction. This in turn can cause hyperuricemia due to the oxidation of purines to uric acid. The hyperuricemia is ameliorated by administration of the xanthine oxidase inhibitor, allopurinol (see p. 417). The agents are concentrated and metabolized in the liver and are excreted into bile and feces. Doses must be modified in patients with impaired hepatic function or biliary obstruction. 

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... 

Usually, one has obtained an estimate for the elimination constant and the distribution volume Vp from a single intravenous injection. These pharmacokinetic parameters, together with the interval between administrations 0 and the single-dose D, then allow us to compute the steady-state peak and trough values. The criterion for an optimal dose regimen depends on the minimum therapeutic concentration (which must be exceeded by and on the maximum safe... 

We consider again the pharmacokinetic parameters of the one-compartment model for a single intravenous injection (eq. (39.6)). 

The simplest case of pharmacokinetics is intravenous injection [1]. In this case the drug is injected directly into the bloodstream. The drug may permeate to different tissues depending on its ability to get across the blood vessel walls and the cellular barriers in the particular tissue targets (Fig. 1). If the drug has small molecular weight and adequate... 

III. FIRST-ORDER PHARMACOKINETICS DRUG ELIMINATION FOLLOWING RAPID INTRAVENOUS INJECTION... 

Mirex was rapidly cleared from the blood of rats following an intravenous injection of 10 mg/kg (Byrd et al. 1982). Mirex blood levels at 8 hours were less than 4% of the levels seen 2 minutes after injection. Pharmacokinetic modeling predicted that intravenously administered mirex was quickly cleared from the blood into a rapidly equilibrating compartment. Over the next several weeks, mirex was redistributed to a slowly equilibrating compartment, which acted as a depot for mirex storage (Byrd et al. 1982). The biological half-life of mirex was estimated to be 435 days (Byrd et al. 1982). 

The results of the in vivo pharmacokinetics are shown in Table 1. DCM-Dex/CDDP conjugate had a significantly longer Pt half-life in the blood after intravenous injection than free CDDP or the OX-Dex/CDDP conjugate. 

The pharmacokinetic calculation of the unidirectional brain uptake rate, after intravenous injection, uses the relation of the brain concentration and the area under the curve of plasma concentration, AUC ... 

The tissue distribution of AS-ODN after a single intravenous injection has been studied extensively in many species including mouse [109], rat [110], monkey [111] and man [112].The majority of pharmacokinetic studies have been performed using phosphorothioated AS-ODNs. In general, the pharmacokinetic profiles of AS-ODNs of varying lengths (up to 20mer) and base compositions are remarkably similar in all species. 

The apparent volume of distribution allows one to estimate the amount of drug in the body at any time after administration based on the concentration (amount=concentrationxvolume). If the plasma concentration of a drug with a VD of 500 litres is 10 ng-mL-1, the amount in the body will be 500000 ml X lO ng or 5 mg. Most pharmacokinetic texts describe several volumes of distribution, e.g. VDarea and VDSS. Following a single rapid intravenous injection, VDarea can be calculated by ... 

Monck, M.A., Mori, A., Lee, D., et al. (2000). Stabilized plasmid-lipid particles Pharmacokinetics and plasmid delivery to distal tumors following intravenous injection. J. Dnug Tanget, 7, 439 152. 

For the case of polyethylene oxide-block-isoprene-block-ethylene oxide) (PEEbtPEO) micelles, the pharmacokinetics and disposition of PEO-PI-PEO in mice was studied after intravenous injection (Rolland et al., 1992). In this study, the cores of the PEO-PI-PEO micelles were cross linked by reaction of isoprene double bonds using UV irradiation along with a photoinitiator. 

We examined the biodistribution of cationic liposomes/pDNA complex following intravenous injection in mice and pharmacokinetically analyzed the data based on the clearance concept (Mahato etal., 1995a, 1997). These analyses showed that the pharmacokinetics of 32P-pDNA complexes depend on their mixing (charge) ratio, the type of cationic and helper lipids (Mahato et al., 1998). When analyzed using radioactivity counting following the injection of the complex prepared with 32P-pDNA, the tissue uptake clearance per g... 

TABLE 5.6 Pharmacokinetic data of parbendazole following single intravenous injection (5 mg/kg) in goats (n = 5)... 

Changes in drug effects are often delayed in relation to changes in plasma concentration. This delay may reflect the time required for the drug to distribute from plasma to the site of action. This will be the case for almost all drugs. The delay due to distribution is a pharmacokinetic phenomenon that can account for delays of a few minutes. This distributional delay can account for the lag of effects after rapid intravenous injection of central nervous system (CNS)-active agents such as thiopental. 

Fig. 2.5 Nonlinear pharmacokinetics ofM-CSF, presented as measured and modeled plasma concentration-time curves (mean SE) after intravenous injection of 0.1 mg/kg (n = 5), 1.0 mg/kg (n = 3), and 10 mg/kg (n = 8) in rats (from [97]).

The administration of a drug by a rapid intravenous injection places the drug in the circulatory system where it is distributed (see section 2.7.1) to all the accessible body compartments and tissues. The one compartment model (Figure 8.3(a)) of drug distribution assumes that the administration and distribution of the drug in the plasma and associated tissues is instantaneous. This does not happen in practice and is one of the possible sources of error when using this model to analyse experimental pharmacokinetic data. 

Pharmacokinetic data show that maximum pharmaceutical exposure occurs generally in the first hour after intravenous injection and, for this reason, a test exposure period of 1 hour is commonly chosen. Nevertheless, this period may not be sufficient for certain cells and drug absorption... 

Pharmacokinetics Amphetamines are completely absorbed from the gastrointestinal tract, metabolized by the liver, and excreted in the urine. Amphetamine abusers often administer the drugs by intravenous injection and by smoking. The euphoria caused by amphetamine lasts 4 to 6 hours, or 4 to 8 times longer than the effects of cocaine. The amphetamines produce addiction—dependence, tolerance and drug-seeking behavior. 

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