Concentration and drugs

Figure 22.1 A. Schema for a physiologically based pharmacokinetic model incorporating absorption in the stomach and intestines and distribntion to various tissues. B. Each organ or tissue type includes representation of perfusion (Q) and drug concentrations entering and leaving the tissue. Fluxes are computed by the product of an appropriate rate law, and permeable surface area accounts for the affinity (e.g., lipophilic drugs absorbing more readily into adipose tissue). Clearance is computed for each tissue based on physiology and is often assumed to be zero for tissues other than the gut, the liver, and the kidneys.

Present in many species of magic mushroom that are eaten raw some toxic mushroom species are visually similar to the psychedelic varieties effects are very variable, depending on the exact species and drug concentration. 

Population PK analysis following a single dose of 30 mg microencapsulated octreotide acetate intramuscularly the PK profile of microencapsulated octreotide acetate was effectively described by the derived population model. The relationship between IGF-1 and drug concentration could be used to guide optimization of therapeutic octreotide dosage regimens... 

Brain delivery of the anticancer drug daunomycin provides an example of the in vivo application of OX26-inununoliposomes [111]. Different formulations of [ H]-daunomycin were i.v. administered to rats either as the free drug or encapsulated in conventional liposomes, sterically-stabilized liposomes, or PEG-conjugated immunohposomes (Table 2.3). Plasma samples were taken at defined time points and after 1 h the animal was killed and drug concentrations in brain tissue were determined. 

Figure 26 compares the spectrum of free MYKO 63 with that of MYKO bound to calf thymus DNA. Both spectra have been normalized to the same Raman scattering intensity and drug concentration. The spectrum of free MYKO 63 was obtained by subtracting the solvent spectrum from the MYKO solution spectrum. The spectrum of the bound drug was obtained by a two-step process (i) the solvent spectrum was subtracted both from the spectrum of the MYKO-DNA complex and from the DNA solution spectrum (ii) subtraction of these two new spectra was... 

Fig. 26. Raman spectra of unbound (A) and bound (B) MYKO 63 after subtraction of calf thymus DNA and NaC104 backgrounds and normalization to the same Raman scattering intensity and drug concentration...

Wode-Helgodt B, Borg S, Fyro B, et al. Clinical effects and drug concentrations in plasma and cerebrospinal fluid in psychotic patients treated with fixed doses of chlorpromazine. Acta Psychiatr Scand 1978 58 149-173. 

The kinetics of DEHP extraction from triple-layered tubing was studied by these authors by varying tube length, flow rate, and drug concentration. Figure 13 shows... 

Behar-Cohen, F.-F., et al. 2002. Trans-scleral coulomb-controlled iontophoresis of methylpredni-solone into the rabbit eye Influence of duration of treatment, current intensity and drug concentration on ocular tissue and fluid levels. Exp Eye Res 74 51. 

Lau, D.T.W., et al. 1994. Effect of current magnitude and drug concentration on iontophoretic delivery of octreotide acetate (Sandostatin ) in the rabbit. Pharm Res 11 1742. 

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. 

Fig. 3.45 Effect of drug concentration on the partition coefficients of tamoxifen (open symbols) and 4-hydroxytamoxifen (closed symbols) in DMPC bilayers (A) and in liposomes of sarcoplasmic reticulum lipids and native membranes (B). Note that the linear correlation between Kp and drug concentration is...

Its volume is 0.27 cm3. Calculate the oral zero-order delivery rate, the period of time (tj for which the drug is delivered at a zero-order delivery rate, and the delivery rate and drug concentration delivered at 1.2 tz. 

Collier HOJ, Cuthbert NJ, Francis DL (1979) Effects of time and drug concentration on the induction of responsiveness to naloxone in guinea pig ileum exposed to normorphine in vitro. Br J Pharmacol 332P-333P... 

The mass balance is calculated by determining volumes by gravimetric and drug concentrations in both the retentate and ultrafiltrate. 

Drugs may also have more than two pKa values, such as polyprotic or polybasic compounds (e.g., minocycline), and such drugs exhibit a complex pH solubility profile. It is essential to know per se pH of the drug solution during preformulation studies. The pH is measured or theoretically calculated if the pKa and drug concentration C are known. The pH of a weak acid or the salt of a weak base and a strong acid can be calculated using the equation... 

In an open study in 164 patients with schizophrenia of the effect of several neuroleptic drugs on the QT interval, the study drugs were given for 21-29 days and three separate electrocardiograms were obtained after steady state had been achieved and drug concentrations were at their maximum (127). The mean changes in the QTC interval were ... 

Although these equations deal with total amounts of drug in the body, the equation C — XjV provides a general relationship between X and drug concentration (C) at any time after the drug dose is administered. Therefore, C can be substituted for X in Equations 2.7 and 2.8 as follows ... 

Assume an experiment in which a group of subjects selected to represent a spectrum of severity of some condition (e.g., renal insufficiency) is given a dose of drug, and drug concentrations are measured in blood samples collected at intervals after dosing. The structural kinetic models used when performing a population analysis do not differ at all from those used for analysis of data from an individual patient. One still needs a model for the relationship of concentration to dose and time, and this relationship does not depend on whether the fixed-effect parameter changes... 

Wagner JG. Kinetics of pharmacologic response I. Proposed relationships between response and drug concentration in the intact animal and man. J Theor Biol 1968 20 173-201. 

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