Tubular secretion, active

The process of reabsorption depends on the HpophiHc—hydrophiHc balance of the molecule. Charged and ioni2ed molecules are reabsorbed slowly or not at all. Reabsorption of acidic and basic metaboHtes is pH-dependent, an important property in detoxification processes in dmg poisoning. Both passive and active carrier-mediated mechanisms contribute to tubular dmg reabsorption. The process of active tubular secretion handles a number of organic anions and cations, including uric acid, histamine, and choline. Dmg metaboHtes such as glucuronides and organic acids such as penicillin are handled by this process. 

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. 

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. 

Drugs that may affect trospium include other anticholinergic agents drugs eliminated by active tubular secretion. 

Drugs that may be affected by trospium include those eliminated by active tubular secretion (eg, digoxin, procainamide, pancuronium, morphine, vancomycin, metformin, and tenofovir). 

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. 

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). 

Coadministration of adefovir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of adefovir or these coadministered drugs. 

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. 

Drugs eliminated by the kidneys Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase serum concentrations of tenofovir and/or the coadministered drug. Some examples include, but are not limited to, acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, and valganciclovir. Drugs that decrease renal function also may increase serum concentrations of tenofovir. 

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. 

Some drugs that are not candidates for active tubular secretion may be metabolized to compounds that are. This is often true for metabolites that are formed as a result of conjugative reactions. Because the conjugates are generally not pharmacologically active, increases in their rate of elimination through active secretion usually have little effect on the drug s overall duration of action. 

Finally, compounds that undergo active tubular secretion also are filtered at the glomerulus (assuming protein binding is minimal). Hence, a reduction in secretory activity does not reduce the excretory process to zero but rather to a level that approximates the glomerular filtration rate. 

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-... 

B) Reduced active tubular secretion of furosemide by the proximal tubule organic acid secretory mechanism... 

The plasma elimination half-life for penciclovir is 2 to 3 hours however, the intracellular half-life of penciclovir triphosphate is 7 to 20 hours in infected cells. Most penciclovir is eliminated unchanged by the kidney via glomerular hltration and active tubular secretion. The plasma half-life is increased in individuals with renal insufficiency. 

Orally administered oseltamivir phosphate is rapidly absorbed and converted by hepatic esterases to oseltamivir carboxylate. Approximately 80% of an oral dose reaches the systemic circulation as oseltamivir carboxylate, with peak plasma concentrations achieved within 2.5 to 5 hours. The plasma elimination half-life of oseltamivir carboxylate is 7 to 9 hours. Elimination of the parent drug and its active metabolite occurs primarily by active tubular secretion and glomerular filtration. 

Intravenous cidofovir is effective for the treatment of CMV retinitis and is used experimentally to treat adenovirus infections. Intravenous cidofovir must be administered with high-dose probenecid (2 g at 3 hours before the infusion and 1 g at 2 and 8 hours after), which blocks active tubular secretion and decreases nephrotoxicity. Cidofovir dosage must be adjusted for alterations in the calculated creatinine clearance or for the presence of urine protein before each infusion, and aggressive adjunctive hydration is required. Initiation of cidofovir therapy is contraindicated in patients with existing renal insufficiency. Direct intravitreal administration of cidofovir is not recommended because of ocular toxicity. 

Emtricitabine (FTC) is a fluorinated analog of lamivudine with a long intracellular half-life (> 24 hours), allowing for once-daily dosing (Figure 49-2). Oral bioavailability of the capsules is 93% and is unaffected by food, but penetration into the cerebrospinal fluid is low. Elimination is by both glomerular filtration and active tubular secretion. 

The thymidine analog stavudine (d4T) (Figure 49-2) has high oral bioavailability (86%) that is not food-dependent. The serum half-life is 1.1 hours, the intracellular half-life is 3.0-3.5 hours, and mean cerebrospinal fluid concentrations are 55% of those of plasma. Excretion is by active tubular secretion and glomerular filtration (Table 49-... 

Tenofovir disopoxilfumarate is a water-soluble prodrug of active tenofovir. The oral bioavailability in fasted patients is approximately 25% and increases to 39% after a high-fat meal. The prolonged serum (12-17 hours) and intracellular half-lives allow once-daily dosing. Elimination occurs by both glomerular filtration and active tubular secretion. 

Oral bioavailability of adefovir dipivoxil is about 59% and is unaffected by meals it is rapidly and completely hydrolyzed to the parent compound by intestinal and blood esterases. Protein binding is low (< 5%). The intracellular half-life of the diphosphate is prolonged, ranging from 5 to 18 hours in various cells this makes once-daily dosing feasible. Adefovir is excreted by a combination of glomerular filtration and active tubular secretion and reguires dose adjustment for renal dysfunction however, it may be administered to patients with decompensated liver disease. 

Interference with renal excretion of drugs that undergo active tubular secretion, especially weak acids. Inhibition of glucuronide conjugation of other drugs. 

Interference with renal excretion of drugs that undergo active tubular secretion. Salicylate renal excretion dependent on urinary pH when large doses of salicylate used. Aspirin (but not other salicylates) interferes with platelet function. Large doses of salicylates have intrinsic hypoglycemic activity. 

The oral bioavailability of stavudine in adults is 86%. Food does not interfere with its absorption. Peak plasma concentrations are reached within lh. The renal elimination accounts for 40% of its clearance. In addition to glomerular filtration, it undergoes active tubular secretion. Sixty percent of the remaining drug is eliminated by endogenous pathways. Its binding to plasma proteins is less than 5%. Stavudine in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection. It causes suppression of HIV and sustained increase in CD4+ cells. 

After oral administration, emtricitabine is rapidly absorbed with a bioavailability of 93%, and it could be administered with or without food. The peak plasma concentration occurs 1-2 h after the oral dose. It does not significantly bind to plasma proteins, and its elimination half-life is 8-10 h. Following glomerular filtration and active tubular secretion, it is primarily excreted unmetabolized in urine. In combination with other antiretroviral agents, emtricitabine is recommended for the treatment of HIV infection. 

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