Total plasma clearance

When clearance is otherwise unspecified, the term clearance is used to mean total plasma clearance, which is the sum of the individual... 

Losartan - Compared with healthy subjects, the total plasma clearance in patients with hepatic insufficiency was about 50% lower and the oral bioavailability was about 2 times higher. A lower starting dose is recommended. 

Abbreviations include t elimination half-life Cl, total plasma clearance and Clj-enab renal clearance. Data expressed as mean values (from James et al., 1998). 

In humans, the mean maximum plasma concentration (Cmax) is 79 ng/mL and the time to achieve Cmax was 2.67 h after a single 3-h infusion of decitabine (1) at 15 mg/m2. At this dose, the volume of distribution at steady state is 148 mL/kg, and the total plasma clearance is 122 L/kg/m2. The terminal half-life is approximately 35 min as decitabine (1) is primarily metabolized in the liver by cytidine deaminase to yield noncytotoxic 5-aza-2 -deoxyuridine. Urinary excretion of unchanged decitabine (1) is low (0.01-0.9% of total dose).13... 

In 16 subjects, meloxicam 15 mg increased plasma lithium concentrations by 21% (range —9 to 59%) and reduced total plasma lithium clearance by 18% (685). 

In the monographs in Part 2, clearance has been included where possible and usually refers to the total plasma clearance (or total whole blood clearance) after intravenous administration. In some instances, the total clearance calculated after oral administration has been included if the drug is known to be well absorbed and is not subject to significant first-pass metabolism. 

For enantiomeric drugs with low organ clearance, differences in renal or hepatic clearance between stereoisomers may reflect their free fraction in the plasma and not real stereoselectivity of the ability of the organ to remove the free enantiomers (intrinsic clearance) from the plasma. Clearance differences between stereoisomers of verapamil and disopyramide may be a function of plasma protein binding differences. In addition, volumes of distribution as well as concentration ratios of stereoisomers in body fluids to total plasma and blood are influenced by plasma protein binding. For example, the larger volume of distribution and greater total body clearance of R-disopyramide compared to the S isomer may be explained by the lower... 

Cholestasis can prolong the action of pancuronium, reducing its plasma clearance by 50%. This may be a result of raised bile salts, reducing the hepatic uptake of pancuronium (which is an important factor contributing to the total plasma clearance in normal patients) (SEDA-6, 130). 

The pharmacokinetic interaction of phenytoin with valproate is complicated (78-80). Initially, the total serum phenytoin concentration falls, because valproate displaces phenytoin from protein binding sites and so the unbound fraction increases, with a consequent increase in clearance. Because of the change in unbound fraction the total plasma concentration effect curve is shifted to the left, and a lower total concentration is as effective as the total phenytoin concentration was in the absence of valproate. However, valproate also inhibits the metabolism of phenytoin and so the serum phenytoin concentration then starts to rise and there is a risk of toxicity. 

From animal investigations hepatic uptake appears to be a factor in the drug s total plasma clearance, but renal excretion seems to be the main route of elimination. Ligation of renal pedicles in dogs (3) resulted in reduced elimination of pipecuronium, with a four-fold increase in mean residence time and a four-fold increase in hepatobiliary elimination, which did not compensate for the loss of urinary excretion. In humans, about 40% of... 

Total plasma clearance and distribution volume of furosemide were much larger in analbuminemic rats compared to normals, whereas the urinary excretion was significantly lower. Injecting the albumin/furo-... 

Plasma cortisol concentration is increased because of decreased metabolic clearance. The plasma concentrations of total triiodothyronine T3), thyroxine (T4), and TSH are considerably reduced, with the thyroxine concentration being most affected. This is partly due to reduced concentrations of thyroxine-binding globulin and prealbumin. 

Brochner-Mortensen J, Giese J, Rossing N. Renal inuUn clearance versus total plasma clearance of Cr-EDTA. Scand J Clin Lab Invest 1969 23 301-5. 

The total plasma concentration of lidocaine is a result of clearance of the drug and is modulated by hepatic function. There is little impact on clearance in renal disease. In situations of decreased organ perfusion, clearance is reduced and increased blood concentrations of lidocaine should be expected reduced dosing is appropriate in these circumstances. The principal binding protein of Hdocaine, AAG, has been demonstrated to accumulate after myocardial infarction. The result of accumulation of this protein is reduction of free lidocaine, which reduces the pharmacological effect of the drug. Lidocaine is usually analyzed by immunoassay, and MEGX and GX by HPLC. 

In Equation 1.2, CL is the total plasma clearance, namely, the fraction of the volume of distribution cleared per unit of time, and is expressed in volume/time. AUC is the area under the concentration versus time curve and is expressed in (concentration)-(time). In other words (Equation 1.3),... 

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