Intravenous injection pharmacokinetic models

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). 

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

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. 

Sontag (1986) Pharmacokinetic Model. An extended multicompartmental model (see Figure 2-9) describing the kinetic behavior of uranium (absorption, distribution, and excretion as a function of time) in the organs of male and female rats was developed using data taken from experiments performed on 13-month-old male and female Sprague-Dawley rats intravenously injected with 1.54 mCi/kg (57 kBq/kg) U-uranyl citrate and sacrificed at 7, 28, 84, 168, or 336 days after injection. 

The pharmacokinetics of thalidasine in a polyphase liposome preparation and in aqueous solution were determined by HPLC in mice following intravenous injection. The blood drug concentration curve fit a two-compartment open model, with the distribution and elimination half-lives being 3.52 and 23.58 minutes, respectively, for the liposome preparation, and 1.293 and 11.12 minutes, respectively, for the aqueous solution [149]. 

Pharmacokinetic evaluations of hypericin 1 and pseudohypericin 2 in experimental animals are restricted to studies in mice. Following intravenous injection of 17.5 mg/kg of synthetically prepared hypericin peak concentrations of 27.8 pg/ml were measured at 10 min and decreasing values could be followed for a period of 240 h (10 ng/ml). The data were well adjusted to a two-compartment model with a distribution phase (ti/2a) of 2 h and an elimination half life (ti/2(3) of 38.5 h. The volume of... 

The simplest pharmacokinetic model (as we shall see in subsequent chapters, this is an intravenous injection of a one-compartment drug eliminated by a first-order process) is described by a single-term exponential equation ... 

Figure 10.2 Pharmacokinetics of intravenous T-20 administration. The graphs show the expected changes in plasma concentration vs time after intravenous administration of a single injection (dashed line) or multiple injections (solid line) of intravenous T-20 (lOOmg/dose). The curves are based on the half-life (1.8 h) and volume of distribution (4.7 L) measured in 17 human volunteers [4] using a one-compartment model (see Equation 7-3). Because of its rapid elimination, multiple doses are needed to maintain the peptide level in the effective range.

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