Drug Metabolism in Drug Design and Development Basic Concepts and Practice

glucuronic acid (UDPGA) for glucuronidation, adenosine 3 0 -phosphate 5 0 phosphosulfate (APPS) for sulfation, glutathione (GSH ...

microcentrifuge at maximum speed. The supernatant is filtered through a spin filter (0.22mm), and transferred into an HPLC injec ...

protein or enzyme should be largely based on the requirement to achieve a measurable overall rate of the metabolism at low micro ...

The nonlinear regression analyses with default options (automatic initial parameter estimations with the constraints ofa>0 an ...

The typical results of such an analysis, in which the data in Table 13.1 were used, are shown in Table 13.2. Intrinsic Clearance ...

If metabolic stability is determined in a suspension of hepatocytes, SF¼ðGcell=WliverÞðWliver=WbodyÞ=Ccell whereGcellis the aver ...

linear metabolite production of up to 45 min of incubation. Nevertheless, the concentrations of the compounds and microsomal pro ...

or ‘‘allosteric’’ effect, which is not uncommon for several important drug-metabolizing CYP members, especially CYP3A4 (Shou et ...

thus, ½ESŠ¼ESk 1 =ðk 2 þk 3 Þ: ð 13 : 11 Þ (k 2 +k 3 )/k 1 is defined as the Michaelis constant (Km). Equation 13.11 becomes [ES ...

2001). For instance, six, or preferably eight, concentrations, covering a range of 0–4 mM, could be considered for the initiatio ...

V/S (ml/min/mg protein) 0.05 0.10 0.15 0.20 (^403020) (nmol/min/mg protein)V 10 0 S (μM) 0 200 400 600 800 1000 (nmol/min/mg pro ...

S (μM) 0 5 10 15 20 25 (nmol/min/mg protein)V 70 60 50 40 30 20 10 0 V/S (ml/min/mg protein) 0 10203040 (pmol/min/mg protein)V 7 ...

possibly CYP3A4, at very high theophylline concentrations. The observed biphasic kinetics, as indicated, could be either due to ...

The apparentVmaxandKmwere determined to be 42.5 nmol/min/mg protein and 180.0mM, respectively, indicating a high capacity with a ...

CYPs involved in the metabolism, one has a high affinity and low capacity (Kappm1¼ 0 : 46 mM;Vappmax1¼ 17 :5 nmol=min=mg protein ...

essential. The typical instrumental settings and operational conditions for LC/ MS/MS systems are described below. An instrument ...

MS Condition The ion source is heated (e.g., 400 50 C) with gas flows. Ion spray voltage is usually high (typically 5000 eV in ...

Thein vitro–in vivocorrelations have been focused on the use of hepatocytes and liver microsomal preparations to predict those p ...

As shown earlier, IfSKm;V=S¼Vmax=Km¼CL 0 int; or CL 0 int¼SðEi=ETÞVi=S;if multiple enzymes are involved: ð^13 :^13 Þ V/Sis in e ...

compounds. However, the outcomes of such remedies have been mixed, providing one of the current challenges forin vitro–in vivoco ...