Dialyzer clearance

The dialysate recovery clearance approach has become the benchmark for determining dialyzer clearance. It can be calculated as ... 

Total clearance during dialysis can be calculated as the sum of the patient s residual clearance during the interdialytic period (CLRES) and dialyzer clearance (CLD) ... 

Metaboiism/Excretion-The terminal elimination half-life for drug bound iron was approximately 1 hour, varying by dose but not by rate of administration. Total clearance was 3.02 to 5.35 L/h. In vitro, less than 1 % of the iron species within sodium ferric gluconate complex can be dialyzed through membranes with pore sizes corresponding to 12,000 to 14,000 daltons over a period of up to 270 minutes. 

Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking metformin, immediately discontinue the drug and promptly institute general supportive measures. Because metformin is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery. 

The main route of elimination is via hepatic excretion into bile some enterohepatic recirculation may occur. The drug has a very low plasma clearance with negligible renal excretion. Neither amiodarone nor its metabolite is dialyzable. 

Hemodialysis Topiramate is cleared by hemodialysis 4 to 6 times greater than in a healthy individual a prolonged period of dialysis may cause topiramate levels to fall below that required to maintain an antiseizure effect. To avoid rapid drops in topiramate plasma concentration during hemodialysis, a supplemental dose of topiramate may be required. The actual adjustment should take into account 1) the duration of the dialysis period, 2) the clearance rate of the dialysis system being used, and 3) the effective renal clearance of topiramate in the patient being dialyzed. 

Renal function impairment A pharmacokinetic study in subjects with renal failure undergoing hemodialysis showed that voriconazole is dialyzed with clearance of 121 mL/min. The IV vehicle, SBECD, is hemodialyzed with clearance of 55 mL/min. A 4-hour hemodialysis session does not remove a sufficient amount of voriconazole to warrant dose adjustment. 

One widely used performance index of hemodialyzers is that of clearance, defined similarly to that of the human kidney. The clearance of a hemodialyzer is the conceptual volume of blood (cm inin ) from which a uremic substance is completely removed by hemodialysis. Let Qg (cm min ) be the blood flow rate through the dialyzer, Qjj fern min ) the dialysate flow rate, and Cg and Cj3 (mgem ) the concentrations of a uremic substance in the blood and the dialysate, respectively, with the subscripts i and o indicating values at the inlet and outlet, respectively. The rate of transfer of the substance in the dialyzer w (mgmin ) is then given as... 

EIGURE 6.1 Plot of dialysis clearance (CL]j) vs. dialyzer blood flow (Q). The theoretical curves were fit to experimental data points to obtain estimates of the permeability coefficient-surface area product (P-S) for each solute. Flow-limited clearance is indicated by the dashed line. The data were generated with a Kolff-Brigham type hemodialysis apparatus. (Reproduced with permission from Renkin EM. Tr Am Soc Artific Organs 1956 2 102-5.)... 

Renkin used Equation 6.1 to estimate permeability coefficients for several solutes from flow and clearance measurements made on the Kolff-Brigham artificial kidney (Figure 6.1). This theoretical analysis seems reasonably consistent with the experimental results. In the Figure/ the dashed line indicates a flow limitation to transport because clearance can never exceed dialyzer blood floW/ a result that is obvious from inspection of Equation 6.1 (i.e./ is never less than 0). 

An analysis of relative dialysis clearance and dialyzer permeability coefficient-surface area products that was made for the closely related compounds procainamide (PA) and N-acetylprocainamide (NAPA) is summarized in Table 6.3. Dialyzer clearance measurements of PA (CLpa) and NAPA (CLmapa)... 

Clearance data obtained by Gibson TP et al. (9), with dialyzer blood flow set at 200 (mL/min) and single-pass dialysate flow at 400 mL/min. 

Single-pass dialyzers are now standard for patient care and clearance calculations suffice for characterizing their performance. However recirculating dialyzers were used in the early days of hemodialysis. 

Equation 6.3 provides an estimate of dialysis plasma clearance (CLp) that is pharmacokinetically consistent with estimates of elimination and intercompartmen-tal clearance that are based on plasma concentration measurements. On the other hand, if the average drug concentration in blood entering the dialyzer (B) is substituted for P, a valid estimate of blood clearance (CLg) is obtained ... 

In contrast with intermittent hemodialysis in which dialyzer blood flow is rate limiting/ diffusive drug clearance during continuous renal replacement therapy is limited by dialysate flow (Qd)/ which typically is only 25 mL/min. Accordingly/ diffusive drug clearance (CLd) is calculated from the equation ... 

Blood is then pumped through the dialyzer, counter-current to the dialysate on the outside of the fibers. Poison clearance occurs hy diffusion of the solute across the porous membrane and into the dialysate. 

Fall in glomerular filtration rate in a rapid and dose related fashion if dose >1 g/m Charcoal hemoperfusion and sequential hemodialysis if severe renal toxicity (significant clearance of methotrexate can be achieved with high-flux dialyzers... 

It is noteworthy that a significant clearance of methotrexate can be achieved with high-flux dialyz-... 

Sera from levamisole-treated mice, rabbits and man were found to yield a dialyzable, complement-unrelated serum factor which did not contain any levamisole metabolites, but which could simulate the biologic effects of levamisole itself. 162 This factor enhanced carbon clearance,169 stimulated lymphocyte proliferation in vitro,187 restored immunological reactivity of athymic mice,179 induced in vitro maturation of mouse pre-T cells,179 stabilized tumor remission and reduced tumor load in experimental systems.162 The factor could not be detected in mice which failed to respond to treatment with levamisole but non-responders reacted to serum factor in a similar way as responders treated with levamisole itself.162 a perhaps identical serum factor could also be induced by the sulfhydryl compound diethyl-dithiocarbamate (65).1 which appears to share some of the immunoenhancing and immunorestorative properties of levcimisole if administered in... 

Dialysis membranes are classified as conventional (standard), high-efficiency, and high-flux. Conventional dialyzers, mostly made of cuprophane, have small pores that limit clearance to relatively smaU molecules such as urea and creatinine. High-efficiency membranes have large surface areas and thus have a greater ability to remove water, urea, and other small molecules from the blood. High-flux... 

The URR is an easy calculation and thus is frequently used to measure the delivered dialysis dose. However, the URR does not account for the contribution of convective removal of urea. The Kt/V is the dialyzer clearance of urea K) in L/h multiplied by the duration of dialysis (/) in hours, divided by the urea distribution volume of the patient (V) in liters. Kt/Vi a unitless parameter that quantitates the fraction of the patient s total body water that is cleared of urea during a dialysis session. Urea kinetic modeling, using special computer software, is the optimal means to determine the Kt/V. Kt/V can also be calculated by using the following equation. ... 

The final component of the dialysis prescription that may affect drug clearance by dialysis is whether or not the patient has anthorized the unit to reuse his or her dialyzer. Currently, more than 75% of all dialysis units in the United States use this procedure to reduce the cost of chronic hemodialysis. The effect of dialysis filter reuse on the clearance of endogenous molecules such as urea, creatinine, and P2-microglobulin has been evaluated for many dialyzers. A decrease in urea and creatinine clearances and an increase in /S2-mictoglobulin clearance was observed with some, but not all, dialyzers. Only one center has evaluated the effect of reuse on drug clearance (cefazolin, ceftazidime, tobramycin, and vancomycin) following the first and tenth use of cellulose acetate, cellulose triacetate, and polysulfone... 

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