Drug elimination active tubular secretion

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). 

Drugs affected by renal function impairment Because entecavir primarily is eliminated by the kidneys, coadministration of entecavir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug. 

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. 

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. 

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. 

The oral availability in the absence of food is 25%, which is increased after a meal that is high in fat content (700-1000 calories containing 40-50% fat). Its plasma half-life is 14-16 h. Tenofovir is not a substrate of the cytochrome P-450 system. After an IV administration, 70-80% is found unchanged in urine. Its elimination is by glomerular filtration and active tubular secretion. Therefore, its concurrent administration with drugs that utilize the same pathway for clearance should be monitored. In combination with other antiretroviral agents, tenofovir is indicated for the treatment of HIV infection. 

B. Pharmacokinetics Several cephalosporins are available for oral use, but most are administered parenterally. Cephalosporins with side-chains may undergo hepatic metabolism, but the major elimination mechanism for drugs in this class is renal excretion via active tubular secretion. Cefoperazone and ceftriaxone are excreted mainly in the bile. Most first- and second-generation cephalosporins do not enter the cerebrospinal Uuid even when the meninges are in-Uamed. 

Pharmacokinetics and clinical use Oral bioavailability of ddl is reduced by food and by chelating agents. The drug is eliminated by glomerular filtration and active tubular secretion, and the dose must be reduced in patients with renal dysfunction. Didanosine is used in HAART combination drug regimens. 

Enantioselectivity in the renal clearance of chiral p2-agonists has been reported for albuterol and terbutaline [112,114,117], After the IV administration of albuterol enantiomers and racemic albuterol, the renal clearance of the individual enantiomers and racemic drug exceeded creatinine clearance, thus implicating active tubular secretion in the urinary elimination of the drug. Renal clearance of R-albuterol was reported to be two- or threefold higher than that of S-albuterol [114]. Since plasma protein binding of albuterol is low [112], the differences in the renal clearance of albuterol enantiomers may be attributed to stereoselectivity in active tubular secretion. 

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. 

The conversion of 6-deoxy penciclovir to penciclovir is catalyzed by aldehyde oxidase. Interactions with other drugs metabolized by this enzyme could occur. Concurrent use with probenecid or other drugs significantly eliminated by active renal tubular secretion may result in increased plasma concentrations of penciclovir. Drug/Food interactions When famciclovir was administered with food, penciclovir Cmax decreased approximately 50%. Because the systemic availability of penciclovir (AUC) was not altered, it appears that famciclovir may be taken without regard to meals. 

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. 

Methotrexate is well absorbed orally and at usual dosages is 50% bound to plasma proteins. The plasma decay that follows an intravenous injection is triphasic, with a distribution phase, an initial elimination phase, and a prolonged elimination phase. The last phase is thought to reflect slow release of methotrexate from tissues. The major routes of drug excretion are glomerular filtration andl active renal tubular secretion. 

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