Drug elimination velocity

The best-known exception to exponential kinetics is the elimination of alcohol (ethanol), which obeys a linear time course (zero-order kinetics), at least at blood concentrations > 0.02 %. It does so because the rate-limiting enzyme, alcohol dehydrogenase, achieves half-saturation at very low substrate concentrations, i.e at about 80 mg/L (0.008 %). Thus, reaction velocity reaches a plateau at blood ethanol concentrations of about 0.02 %, and the amount of drug eliminated per unit of time remains constant at concentrations above this level. 

The neutrophil-mediated clearance was expressed as a Michaelis-Menten function, because G-CSF receptor binding is subject to saturation. The product of kcat and the ratio of ANC and ANC at baseline is the maximum velocity of drug elimination from this pathway, km is the Michaelis constant, and C is the pegfilgrastim concentration. CL2 denotes the linear clearance pathway. 

Clearance represents the ability of drug elimination and is defined by dividing the velocity of elimination by the blood or plasma concentration of a drug (Buxton, 2006). Based on the physiological PK model theory, the CLorg,biood is described by Eq. (6.1) ... 

By definition, the intrinsic clearance (CLjnt) is calculated by dividing the elimination velocity of a drug (v) by the drug concentration at the target site (Jusko, 1992). The activity of metabolizing enzymes and drug transporters can also be determined as the intrinsic clearance by in vitro experiments. As discussed later, we can extrapolate CLjnt values determined in vitro to in vivo CLjnt values. 

Procainamide INa (primary) and IKr (secondary) blockade Slows conduction velocity and pacemaker rate prolongs action potential duration and dissociates from INa channel with intermediate kinetics direct depressant effects on sinoatrial (SA) and atrioventricular (AV) nodes Most atrial and ventricular arrhythmias drug of second choice for most sustained ventricular arrhythmias associated with acute myocardial infarction Oral, IV, IM eliminated by hepatic metabolism to /V-acetylprocainamide (NAPA see text) and renal elimination NAPA implicated in torsade de pointes in patients with renal failure Toxicity Hypotension long-term therapy produces reversible lupus-related symptoms... 

Following their metabolic transformation, sulfonamides are eliminated in urine, feces, bile, and milk. However, the kidney is the organ primarily involved in the excretion of these drugs. Sulfonamide residues deplete from body tissues and fluids with widely variable velocity that depends on many factors including the nature of the compound, its formulation and the route of administration, and the animal species. Nevertheless, sulfonamide residues eliminate much earlier from liver, kidney, and milk than from muscle and fat. Withdrawal periods in meat and milk differ, therefore, for each sulfonamide. 

Steady state the hepatic intrinsic clearance of pravastatin, a substrate for OATP2 and MRP2 (Tokui et al., 1999 Yamazaki et al., 1997), was regulated by the uptake process, followed by rapid metabolism and/or biliary excretion with minimal efflux to the systemic circulation in rats after infusion. The total hepatic elimination rate at steady state exhibited Michaelis-Menton saturation with the drug concentration and the and V ax obtained in rats with different mathematical models (i.e., well stirred, parallel tube, and dispersion models) were comparable with the initial uptake velocity measured from in vitro hepatocytes (Tokui et al., 1999). 

Vcirc actual circulatory volume Vmax maximal velocity (rate) of elimination in non-linear (Michaelis-Menten) kinetics Vss (Vdss) for a two-compartment model drug, the apparent total volume of distribution at steady state Vtbw volume of total body water X the mass, or amount, of drug present in the body at time t this does not include any drug that may be present in the gastrointestinal tract... 

Please note that the organ and body clearance values in this chapter (i.e., CL/, CLorai, CLorg, CL,., and CLtot) are defined for the plasma concentration, which are given by the velocity of elimination divided by the plasma drug concentration, except for CLorg,blood, which is defined for the blood drug concentration. 

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