Drug concentration determination

Fig. 1. Blood—drug concentration curve used to determine bioavailabiLitv and bioequivalence. C is the maximum dmg concentration in the blood and corresponds to some The AUC (shaded) represents the total amount of orally adininistered dmg the time from points A to B represents dmg onset, from points B to D, the duration MEC = minimum effective concentration MTC = minimum toxic concentration and TI = therapeutic index.

IC50 was determined as the drug concentration which inhibited 50 % of the specific binding of the ligand. 

In patients with a history of AED use, a baseline serum concentration may be useful to determine if the drug concentration is below the desired range and if a loading dose is needed. Albumin levels, renal function tests, and liver function tests can also be helpful when assessing antiepileptic therapy. 

Here, we briefly describe the automated Caco-2 assay used at the research site in AstraZeneca R D Molndal. The solubility of the test compounds is measured (or theoretically predicted) before they are run in the Caco-2 assay. In order to be able to make correct determinations of the permeability coefficient, the substance must be dissolved when added to cell monolayer in the transport experiment. Compounds with insufficient solubility are therefore not tested. We generally apply a test concentration of 10 pM, but in specific projects or under certain circumstances a concentration of only 1 pM is applied. The test compounds are first prepared in DM SO solution (1 mM) on a parent plate and are then diluted in transport buffer to give a final drug concentration of 10 pM (solution containing 1% DMSO) when added to the cell monolayers. 

Fig. 5.3. Relationship between the oral fraction basolateral Papp values were determined at absorbed in humans and apparent permeability drug concentrations of 10-500 pM at pH 6.5/ coefficients obtained in Caco-2 cell monoalyers 7.4 or 7.4/7.4 on the apical/basolateral sides of at two different pH conditions. Mean apical to the cell monolayers.

If the unbound drug concentrations in plasma are higher than their K values on the transporters, then transporter function may be significantly affected [106], Following a pharmacokinetic analysis of the effect of probenecid on the hepatobiliary excretion of methotrexate, it has been shown the extent of an in vivo drug-drug interaction can be quantitatively predicted from the kinetic parameters for transport across the sinusoidal and bile canalicular membranes determined in vitro [107]. 

Membrane Partitioning Determines Drug Concentration at Half-Maximum P-gp-ATPase Activation, Km... 

Fig. 20.1. Correlation between the air/water partition coefficient, Kaw, determined from measurements of the surface pressure as a function of drug concentration (Gibbs adsorption isotherm) in buffer solution (50 mM Tris/HCI, containing 114 mM NaCI) at pH 8.0 and the inverse of the Michaelis Menten constant, Km obtained from phosphate release...

Goger and Gokcen [19] developed a quantitative method for the determination of miconazole in cream formulations that contain benzoic acid as preservative by second order derivative spectrophotometry. The procedure was based on the linear relationship in the range 100—500 pg/mL between the drug concentration and the second-derivative amplitudes at 276 nm. Results of the recovery experiments performed on various amounts of benzoic acid and the determination of miconazole in cream confirmed the applicability of the method to complex formulations. 

A specific and sensitive fluorimetric method was proposed by Al-Majed for the determination of (7))-penicillamine in its pure state and in its dosage forms [24], The method is based on the coupling between (/))-penicillamine and 4-fluoro-7-nitroben-zo-2-oxa-1,3-diazole, and analysis of the fluorescent product was measured at an excitation wavelength of 465 nm and an emission wavelength of 530 nm. The fluorescence intensity was found to be a linear function of the drug concentration over the range of 0.6-3 pg/mL, and the detection limit was 2 ng/mL (13 nM). 

---