Excretion tubular secretion

Metabolism/Excretion- Metformin is excreted unchanged in the urine and does not undergo hepatic metabolism or biliary excretion. Tubular secretion is the major route of elimination. The elimination half-life is approximately 17.6 hours. 

Several hydrophilic, anionic technetium complexes can be used to perform imaging studies of the kidneys. Tc-Mertiatide (Fig. 5a) is rapidly excreted by active tubular secretion, the rate of which is a measure of kidney function. Tc-succimer (Fig. 5b), on the other hand, accumulates in kidney tissue thus providing an image of kidney morphology. 

Technetium-99m mertiatide (A/-[Ai-[A/-[(benzoylthio)acetyl]glycyl]glycine) is a renal imaging agent. It is excreted by the kidneys via active tubular secretion and glomerular filtration. The kit vial is reconstituted by using 740—3700 MBq (20—100 mCi) of Tc pertechnetate and boiling for 10 minutes. 

The co-administration of drugs which inhibit the transporters involved in renal tubular secretion can reduce the urinaty excretion of drugs which are substrates of the transporter, leading to elevated plasma concentrations of the drugs. For example, probenecid increases the plasma concentration and the duration of effect of penicillin by inhibiting its renal tubular secretion. It also elevates the plasma concentration of methotrexate by the same mechanism, provoking its toxic effects. 

As nephron mass decreases, both the distal tubular secretion and GI excretion are increased because of aldosterone stimulation. Functioning nephrons increase FEK up to 100% and GI excretion increases as much as 30% to 70% in CKD,30 as a result of aldosterone secretion in response to increased potassium levels.30 This maintains serum potassium concentrations within the normal range through stages 1 to 4 CKD. Hyperkalemia begins to develop when GFR falls below 20% of normal, when nephron mass and renal potassium secretion is so low that the capacity of the GI tract to excrete potassium has been exceeded.30... 

The renal excretion of drugs depends on glomerular filtration, tubular secretion, and tubular absorption. A twofold increase in glomerular filtration occurs in the first 14 days of life [36], The glomerular filtration rate continues to increase rapidly in the neonatal period and reaches a rate of about 86 mL/min per 1.73 m2 by 3 months of age. Children 3-13 years of age have an average clearance of 134 mL/min per 1.73 m2 [37]. Tubular secretion approaches adult values between 2 and 6 months [11], There is more variability observed in maturation of tubular reabsorption capacity. This is likely linked to fluctuations in urinary pH in the neonatal period [38],... 

Tubular secretion is the transfer of substances from the peritubular capillaries into the renal tubule for excretion in urine. This process is particularly important for the regulation of potassium and hydrogen ions in the body it is also responsible for removal of many organic compounds from the body. These may include metabolic wastes as well as foreign compounds, including drugs such as penicillin. Most substances are secreted by secondary active transport. 

NRC 1993 Vieira et al. 1996). Whether differences in xenobiotic metabolism make the child more or less suseeptible also depends on whether the relevant enzymes are involved in activation of the parent compound to its toxic form or in detoxification. There may also be differences in excretion, particularly in the newborn who has a low glomerular filtration rate and has not developed efficient tubular secretion and resorption capacities (Altman and Dittmer 1974 NRC 1993 West et al. 1948). Children and adults may differ in their capacity to repair damage Irom chemical insults. Children also have a longer lifetime in which to express damage Irom chemicals this potential is particularly relevant to cancer. 

The absorption and excretion of carbenicillin in man has been reported [396]. The antibiotic is not absorbed intact from the gut intramuscular injection (which is painful) often provides adequate serum levels (approximately 20 Mg/ntl) but infections with Pseudomonas strains having minimum inhibitory concentrations up to, or higher than, 100 Mg/ml require intravenous thbrapy to achieve such levels. No evidence of active metabolite formation has been obtained. Marked reductions in the half-life (and serum levels) of carbenicillin follow extracorporeal dialysis or peritoneal dialysis, the former producing the most striking effect [397]. These results were, of course, obtained in patients with severe renal failure. Patients with normal renal function rapidly eliminate the drug but, as with all penicillins, renal tubular secretion can be retarded by concurrent administration of probenecid. 

In calves and cows, SDM was excreted by glomerular filtration minus tubular reabsorption its renal clearance was urine flow correlated, and amounts to half of the creatinine clearance. The SCH2OH hydroxy metabolite was excreted by glomerular filtration and partly by tubular secretion, whereas both Na-SDM and SOH were excreted predominantly by tubular secretion (15 . The main metabolite in urine SCH2OH was 23 to 55 % of the administered dose (Table III). The urine concentration—time curves for SDM and its metabolites are illustrated in Figure 7 for a high SDM dosage. 

Walton et al. (2004) determined the extent of interspecies differences in the internal dose of compounds, which are eliminated primarily by renal excretion in humans. Renal excretion was also the main route of elimination in the test species for most of the compounds. Interspecies differences were apparent for both the mechanism of renal excretion (glomemlar filtration, tubular secretion, and/or reabsorption), and the extent of plasma protein binding. Both of these may affect renal clearance and therefore the magnitude of species differences in the internal dose. For compounds which were eliminated unchanged by both humans and the test species, the average difference in the internal dose between humans and animals were 1.6 for dogs, 3.3 for rabbits, 5.2 for rats, and 13 for mice. This suggests that for renal excretion the differences between humans and the rat, and especially the mouse, may exceed the fourfold default factor for toxicokinetics. 

In rats ammonium perfluorooctanoate induced hepatomegaly that was more pronounced in the male than in the female. Male rats are thought to be more sensitive to the toxic effects of ammonium perfluorooctanoate because of their slower excretion rate. The rapid excretion by female rats is due to active renal tubular secretion, which is considered to be hormonally controlled by estradiol and testosterone levels. The hepatomegaly was hypertrophic rather than hyperplastic and involved proliferation of peroxisomes. 

Some drugs, such as the two-substituted thiodiazole and acetazolamide (Diamox), increase serum uric acid by stimulating uric acid synthesis (K9). Others, such as chlorothiazide (Diuril), increase uric acid retention by decreasing uric acid excretion (K9). Hydrochlorothiazide inhibits tubular secretion and has been shown to increase pretreatment mean uric acid values from 6.5 mg/100 ml to 10.3 mg/100 ml by the third treatment day. In a patient with gout, the level increased from 8 mg/100 ml to 12 mg/100 ml (H6). In a single case a paradoxical hypouricemia occurred (H6). 

Excretion - The plasma half-life for trospium following oral administration is approximately 20 hours. After administration of oral trospium, the majority of the dose (85.2%) was recovered in feces and a smaller amount (5.8%) was recovered in urine 60% of the radioactivity excreted in urine was unchanged trospium. The mean renal clearance for trospium (29.07 L/h) is 4-fold higher than average glomerular filtration rate, indicating that active tubular secretion is a major route of elimination for trospium. There may be competition for elimination with other compounds that also are renally eliminated. 

Probenecid also inhibits the tubular secretion of most penicillins and cephalosporins and usually increases plasma levels by any route the antibiotic is given. Pharmacokinetics Probenecid is well absorbed after oral administration and produces peak plasma concentrations in 2 to 4 hours. It is highly protein bound (85% to 95%). Probenecid is excreted in the urine primarily as metabolites. 

Metabolism/Excretion- Memantine undergoes little metabolism, with the majority (57% to 82%) of an administered dose excreted unchanged in urine. Memantine has a terminal elimination half-life of about 60 to 80 hours. Renal clearance involves active tubular secretion. 

Excretion - Penicillins are excreted largely unchanged in the urine by glomerular filtration and active tubular secretion. Nonrenal elimination includes hepatic inactivation and excretion in bile this is only a minor route for all penicillins except nafcillin and oxacillin. Excretion by renal tubular secretion can be delayed by coadministration of probenecid. Elimination half-life of most penicillins is short (no... 

Metabolism/Excretion - In healthy subjects, aztreonam is excreted in the urine about equally by active tubular secretion and glomerular filtration. Approximately 60% to 70% of an IV or IM dose was recovered in the urine by 8 hours recovery was complete by 12 hours. 

It does not inhibit cytochrome P450. Gatifloxacin is excreted as unchanged drug primarily by the kidney. Gatifloxacin undergoes glomerular filtration and tubular secretion. 

Norfloxacin - Absorption is rapid. Food or dairy products may decrease absorption. Steady-state norfloxacin levels will be attained within 2 days of dosing. Norfloxacin is eliminated through metabolism, biliary excretion, and renal excretion. Renal excretion occurs by glomerular filtration and tubular secretion. In healthy elderly volunteers, norfloxacin is eliminated more slowly because of decreased renal function. In patients with Ccr rates 30 mL/min/1.73 m or less, the renal elimination decreases so that the effective serum half-life is 6.5 hours dosage alteration is necessary. 

Approximately 80% to 90% of IV foscarnet is excreted unchanged in the urine of patients with normal renal function. Both tubular secretion and glomerular filtration account for urinary elimination of foscarnet. 

Excretion - The major route of elimination of valganciclovir is by renal excretion as ganciclovir through glomerular filtration and active tubular secretion. Systemic clearance of IV administered ganciclovir was about 3.07 mL/min (n = 68) while renal clearance was about 2.99 mL/min/kg (n = 16). 

Excretion - Absorbed oseltamivir is primarily (more than 90%) eliminated by conversion to oseltamivir carboxylate. Plasma concentrations of oseltamivir declined with a half-life of 1 to 3 hours in most subjects after oral administration. Oseltamivir carboxylate is not further metabolized and is eliminated in the urine. Plasma concentrations of oseltamivir carboxylate declined with a half-life of 6 to 10 hours in most subjects. Oseltamivir carboxylate is eliminated entirely (more than 99%) by renal excretion. Renal clearance (18.8 L/h) exceeds glomerular filtration rate (7.5 L/h) indicating that tubular secretion occurs, in addition to glomerular filtration. Less than 20% of an oral dose is eliminated in feces. 

Metabolism/Excretion - Following a single oral dose of tenofovir, the terminal elimination half-life is approximately 17 hours. Tenofovir is eliminated by a combination of glomerular filtration and active tubular secretion. 

Renal clearance in cancer patients has varied from about 4 2 to 10 6 mL/min/m and 10% and 30% is excreted unchanged in the urine. Considering the free fraction of trimetrexate, active tubular secretion may possibly contribute to the renal clearance. 

Any drug known to be largely excreted by the kidney that has a body half-life of less than 2 hours is probably eliminated, at least in part, by tubular secretion. Some drugs can be secreted and have long half-lives, however, because of extensive passive reabsorption in distal segments of the nephron (see Passive Diffusion, earlier in the chapter). Several pharmacologically active drugs, both anions and cations, known to be secreted are listed in Table 4.5. 

It is important to appreciate that these tubular transport mechanisms are not as well developed in the neonate as in the adult. In addition, their functional capacity may be diminished in the elderly. Thus, compounds normally eliminated by tubular secretion will be excreted more slowly in the very young and in the older adult. This age dependence of the rate of renal drug secretion may have important therapeutic implications and must be considered by the physician who prescribes drugs for these age groups. 

Most drugs act by reducing active transport rather than by enhancing it. Thus, drugs that promote uric acid loss (uricosuric agents, such as probenecid and sulfinpyrazone) probably inhibit active urate reabsorption, while pyrazinamide, which reduces urate excretion, may block the active tubular secretion of uric acid. A complicating observation is that a drug may primarily inhibit active reabsorption at one dose and active secretion at another, frequently lower, dose. For example, small amounts of salicylate will decrease total urate ex-... 

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