Metabolic clearance rate

When a drug is eliminated by both metabolism and urinary excretion, it is possible to calculate the metabolic clearance rate (MCR) by the difference between TCR and RCR ... 

C. In adolescent males, testicular testosterone production dramatically rises from prepuberal levels and then declines into adulthood. However, with advancing adulthood there is a drop in the metabolic clearance rate of testosterone, increasing the length of time that testosterone remains in the serum. Evidence of a relatively constant level of serum testosterone is seen in the relative constant levels of urinary 17-ketosteroids, a metabolite of testosterone, from the second to the fifth decade of life. 

In patients with longstanding hypothyroidism and those with ischemic heart disease, rapid correction of hypothyroidism may precipitate angina, cardiac arrhythmias, or other adverse effects. For these patients, replacement therapy should be started at low initial doses, followed by slow titration to full replacement as tolerated over several months. If hypothyroidism and some degree of adrenal insufficiency coexist, an appropriate adjustment of the corticosteroid replacement must be initiated prior to thyroid hormone replacement therapy. This prevents acute adrenocortical insufficiency that could otherwise arise from a thyroid hormone-induced increase in the metabolic clearance rate of adrenocortical hormones. 

Corticotropin can promote the development of a more or less pronounced Cushingoid state. Corticotropin also increases the metabolic clearance rate of cortisol, aldosterone, and desoxycorticosterone (SEDA-1, 282). 

Serum hormone concentrations reflect both the rate of secretion and clearance by peripheral tissues. In parallel with our studies on prolactin secretion we have evaluated the effects of dietary fat on the metabolic clearance rate of prolactin. Rats were initially treated with ergocryptine to suppress endogenous prolactin secretion. We then measured the disappearance of immuno-reactive prolactin from the sera after a single intravenous injection of prolactin. No significant effect of dietary fat on the clearance of prolactin was observed (Figure 4). 

Figure 4. Metabolic clearance rate of prolactin in female rats fed diets containing 4 (low fat) or 20% (high fat) corn oil for 18 weeks.

Formation of sulfates [328] is relatively reversible. This may be due to the fact that the metabolic clearance rate [318] of sulfates is relatively low [389] and their renal excretion inefficient [4]. The conversion of dehydroepiandrosterone sulfate in vivo to androsterone and etiocholanolone glucuronide was demonstrated by Lieberman and co-workers, who administered isotopically labeled dehydroepiandrosterone sulfate and isolated labeled androsterone and etiocholanolone from glucuronicase-hydrolyzed urine [303]. Since in another study by Lieberman [174], the transconjugation from dehydroepiandrosterone sulfate to dehydroepiandrosterone glucuronide without free dehydroepiandrosterone intermediate was declared to be improbable, in vivo equilibrium between dehydroepiandrosterone sulfate and dehydroepiandrosterone seems probable [303]. 

Gant NF, Madden JD, Siteri PK, MacDonald PC. The metabolic clearance rate of dehydroisoandrosterone sulfate. III. The effect of thiazide diuretics in normal and future pre-eclamptic pregnancies. Am J Obstet Gynecol 1975 123(2) 159-63. 

A prolonged insulin action can also be achieved by encapsulation of insulin in liposomes before subcutaneous injection. The extended hypoglycaemic response is believed to be a result of a lower metabolic clearance rate. Currently, the encapsulation efficiency, however, is only 5% (Spangler, 1990). Further investigations are needed. 

The metabolic clearance rate of PSA follows a two-compartment model with initial half-lives of 1.2 and 0.75 hours for free PSA and total PSA and subsequent half-lives of 22 and 33 hours. Because of this relatively long half-life, 2 to 3 weeks may be necessary for the serum PSA to return to baseline levels after certain procedures, including transrectal biopsy, transrectal ultrasonography, transurethral resection of the prostate, and radical prostatectomy. Prostatitis and acute urinary retention can also elevate PSA concentration. Although the digital rectal examination has no clinically important effects on serum PSA levels in most patients, in some it may lead to a twofold elevation. 

Samojlik E, Kirschner MA, Silber D, Schneider G, Ertel NH. Elevated production and metabolic clearance rates of androgens in morbidly obese women. J Clin Endocrinol Metab 1984 49 949-54,... 

Subsequently Tait (Tl) introduced the metabolic clearance rate (MCR) as a combination of Pearlman s approach with Homer Smith s well-known concept of renal clearance. In this treatment the clearance rate of a hormone from the blood is expressed as the (conceptual) volume of blood which would contain the amount of steroid cleared from the (actual) blood per unit time. 

Duby A K, Hanukoglu A, Hansen B C, et al. (1988). Metabolic clearance rates of synthetic human growth hormone in lean and obese male rhesus monkeys. J. Clin. Endoc. Metab. 67 1064-1067. 

Table 46.3. Estrogenic Affinity for Binding Proteins and Metabolic Clearance Rate (11,12)...

Estrogen RBA to SHBG % Bound to SHBG % Bound to Albumin Metabolic Clearance Rate (litter/day/m )... 

In the serum, progesterone is bound to either cortisol binding globulin or albumin, with only a small fraction being freely available. The metabolic clearance rate for progesterone is 2,100 to 2,500 L/day, for which protein binding has no role. 

Indicator of intrinsic low-dose metabolic clearance rate... 

Daily production rate (pg/day) = plasma concentration (pg/ml) x metabolic clearance rate (ml/ day) [25],... 

Svendsen TL, Kristensen MB, Hansen JM, SkovstedL. The influence of disulfiram on the half life and metabolic clearance rate of diphenylhydantoin and tolbutamide in man. Eur J Clin Phamacol( 976) 9,439-41. 

Most screens are project-specific but some, such as simple measures of metabolic clearance rate, are available to all projects. 

The experimental data of plasma and urine radioactivities were analyzed by the non-compartmental approach (Rescigno and Gurpide, 1973), as described in details previously (Bianchi et al., 1979). The formulas utilized in this approach allow to determine the following parameters of uric acid kinetics total metabolic clearance rate (MCR), mean residence time of the tracer, total distribution volume (TDV, plasma equivalent), fractional catabolic rate (FCR, relative to TDV), and clearance rate of C-uric acid via the renal route (MCR] ). The total turnover rate (TR) and the total pool of exchangeable uric acid are then obtained as the product of, respectively MCR or TDV by the plasma urate concentration. The extrarenal disposal of uric acid (bacterial uricolysis in the gut, skin desquamation) is determined as the difference between the total metabolic clearance rate and the clearance rate of uric acid through the kidney route. 

Antidiabetic EGb-761 and G-B Ingestion of G. biloba extract by an NIDDM subject may increase the hepatic metabolic clearance rate of not only insulin but also the hypoglycemic agents protect beta cells [29-31]... 

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