Urinary excretion/elimination

The pharmacokinetics of azacitidine shows that it is rapidly absorbed after s.c. administration with the peak plasma concentration occurring after 0.5 h. The bioavailability of s.c. azacitidine relative to i.v. azacitidine is approximately 89%. Urinary excretion is the primary route of elimination of azacitidine and its metabolites. The mean elimination half-lives are about 4 h, regardless of i.v. or s.c. administration. 

The primary urinary metabolites of trichloroethylene in humans are trichloroethanol, trichloroethanol glucuronide, and TCA (Monster et al. 1979 Nomiyama and Nomiyama 1971 Sato et al. 1977). The halftime for renal elimination of trichloroethanol and trichloroethanol glucuronide has been determined in several studies to be approximately 10 hours following trichloroethylene exposure (Monster et al. 1979 Sato et al. 1977). The urinary excretion of TCA is much slower, and data from several studies indicate that the halftime of urinary TCA is approximately 52 hours because the metabolite is very tightly and extensively bound to plasma proteins (Monster et al. 1976 Sato et al. 1977). 

Urine is the principal excretory route for elimination of diisopropyl methylphosphonate after oral administration to mice, rats, pigs, mink, or dogs (Hart 1976 Snodgrass and Metker 1992 Weiss et al. 1994). However, the rate of excretion differs among species. Peak urinary excretion of a single oral dose of 225 mg/kg [14C]-radiolabeled diisopropyl methylphosphonate occurred at 6 hours in mice,... 

Studies with rats treated orally with triaryl or trialkyl phosphate esters (which may be found in organophosphate ester hydraulic fluids) indicate that these compounds and their metabolites are readily excreted in the urine, bile, feces and, to a limited extent, in expired air (Kurebayashi et al. 1985 Somkuti and Abou-Donia 1990a Suzuki et al. 1984a Yang et al. 1990). Urinary excretion of metabolites appears to be the predominant elimination route in rats for tri-ort/zo-cresyl phosphate and tri-para-cresyl phosphate, but biliary excretion of parent material and metabolites is also important (Kurebayashi et al. 1985 NTP... 

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 ... 

Thus, the overall elimination rate constant (ke[) here is the sum of the urinary excretion rate constant (ke) and the metabolism rate constant (km) ... 

At the present time no simple relationship exists between clinical measurements of liver function and the value of km. Fortunately, kidney function can be measured quantitatively using standard clinical tests, and it is directly related to ke for a number of drugs. Great success has been achieved in using kidney clearance measurements to predict the biological half-lives of a number of drugs. This is best illustrated with a drug that is eliminated exclusively by urinary excretion. 

The usual goal of an oral sustained-release product is to maintain therapeutic blood levels over an extended period. To achieve this, drug must enter the circulation at approximately the same rate at which it is eliminated. The elimination rate is quantitatively described by the half-life (t /2). Each drug has its own characteristic elimination rate, which is the sum of all elimination processes, including metabolism, urinary excretion, and all other processes that permanently remove drug from the bloodstream. 

Organic Lead. Urinary lead levels were elevated for 4 days in a man accidentally exposed to an unknown quantity of tetramethyl lead (Gething 1975). Exhalation of the tetraalkyl lead compounds following inhalation exposure is a major route of elimination in humans. At 48 hours postexposure, 40% and 20% of the initially inhaled tetramethyl and tetraethyl lead doses, respectively, were exhaled with low urinary excretion (Heard et al. 1979). 

Mihaly et al. [128] identified the carboxylic acid derivative of primaquine as a major plasma metabolite. After oral administration of 45 mg of primaquine to healthy volunteers, absorption of the drug was rapid, with peak primaquine levels of 153.3 ng/mL at 3 h, followed by an elimination half-life of 7.1 h, systemic clearance of 21.1 L/h, volume of distribution of 205 L and cumulative urinary excretion of 1.3% of the dose. Primaquine was converted rapidly to the carboxylic acid metabolic, which achieved peak levels of 1427 ng/mL at 7 h. 

The answer is b. (Katzungr pp 806—807J Rifampin induces cytochrome P450 enzymes, which causes a significant increase in elimination of drugs, such as oral contraceptives, anticoagulants, ketoconazole, cyclosporine, and chloramphenicol. It also promotes urinary excretion of methadone, which may precipitate withdrawal. 

During a 16-day vacation and plant shutdown, urinary excretion accounted for 90% elimination in those with high initial PCP levels (i.e., >0.1 mg/L) to 67% elimination in those with initial urinary levels of 0.02-0.1 mg PCP/L, and to 34% reduction in workers with <0.02 mg/L Tb 1/2 was estimated at 33 h in urine and 30 h in plasma (Kalman and Horstman 1983)... 

Lipniak-Gawlik, M. 1998. Effect of polycyclic aromatic hydrocarbons on the elimination kinetics of pyrene and the urinary excretion profile of 1-hydroxypyrene in the rat. Jour. Toxicol. Environ. Health 55A 503-516. 

About two-thirds of the uric acid produced each day is excreted in the urine. The remainder is eliminated through the GI tract after enzymatic degradation by colonic bacteria. A decline in the urinary excretion of uric acid to a level below the rate of production leads to hyperuricemia and an increased miscible pool of sodium urate. 

Peak plasma levels are reached about 1.5 h after oral ingestion, the maximum concentrations being in the order of 2 - 3 ng equivalents/ml (parent drug + metabolites) for an oral 1 mg dose. The elimination from the plasma is biphasic and proceeds with mean half-lives of 6 h (a-phase) and 50 h ((3-phase). Similar elimination half-lives are obtained from the urinary excretion. The cumulative renal excretion is practically the same after oral and intravenous administration and amounts to 6 - 7 % of the radioactivity dosed. The main portion of the dose, either oral or intravenous, is eliminated by the biliary route into the faeces. The kinetics of bromocriptine has been demonstrated to be linear in the oral dose range from 2.5 to 7.5 mg. 

When rats were given 2 mg CN /kg [14C]potassium cyanide, urinary excretion of radioactivity reached 47% of the dose within 24 hours following administration (Farooqui and Ahmed 1982). When [ 14C] sodium cyanide was injected subcutaneously into rats at a level of 8.3 pmol, no difference in radioactivity eliminated was observed between the group pretreated for 6 weeks with a diet containing 0.7 mg CNTkg as potassium cyanide and their matching controls (Okoh 1983). Most of the radioactivity was detected in... 

The main organ involved in PCB metabolism and excretion in fish is the liver. Metabolism of PCBs in fish liver homogenates has been demonstrated (29,30,32) and PCB metabolites are excreted into bile (25,28,34). What is not known is extent to which PCB metabolites excreted in bile are eliminated in feces. Also the role of kidneys, gills, intestine and skin in PCB elimination in fish has not been fully elucidated. The only study on urinary excretion of PCBs was in dogfish sharks and revealed that urine was not a major route of elimination (28). 

Following IV administration of iron sucrose, it is dissociated into iron and sucrose by the reticuloendothelial system. The sucrose component is eliminated mainly by urinary excretion. Some iron also is eliminated in the urine. 

Pharmacology Succimer is an orally active, heavy metal chelating agent it forms water soluble chelates and, consequently, increases the urinary excretion of lead. Pharmacokinetics In a study in healthy adult volunteers, after a single dose of 16, 32, or 48 mg/kg, absorption was rapid but variable, with peak blood levels between 1 and 2 hours. Approximately 49% of the dose was excreted 39% in the feces, 9% in the urine, and 1 % as carbon dioxide from the lungs. Because fecal excretion probably represented nonabsorbed drug, most of the absorbed drug was excreted by the kidneys. The apparent elimination half-life was about 2 days. 

Renal elimination is primarily by glomerular filtration. Parent drug and metabolites are excreted primarily by the kidney however, urinary excretion... 

Excretion - The terminal elimination half-life is between 5 and 6 days following inhalation. After dry powder inhalation, urinary excretion is 14% of the dose, the remainder being mainly nonabsorbed drug in the gut, which is eliminated via the feces. The renal clearance of tiotropium exceeds the Ccr, indicating active secretion into the urine. After chronic, once-daily inhalation by COPD patients, pharmacokinetic steady state was reached after 2 to 3 weeks with no accumulation thereafter. 

Pharmacokinetics Non-ergot dopamine agonists are rapidly absorbed. The absolute bioavailability is more than 90%. Steady-state concentrations are achieved within 2 days of dosing. Terminal half-life is about 8 hours (about 40 minutes for apomorphine) in young healthy volunteers and about 12 hours in elderly volunteers. Urinary excretion is the major route of elimination. 

Pharmacokinetics Bioavailability of tablet vs liquid is approximately 90%. Diphenoxylate is rapidly, extensively metabolized to diphenoxylic acid (difenoxine), the active major metabolite. Elimination half-life is approximately 12 to 14 hours. An average of 14% of drug and metabolites are excreted over 4 days in urine, 49% in feces. Urinary excretion of unmetabolized drug is less than 1% difenoxine plus its glucuronide conjugate constitutes approximately 6%. 

Metabolism/Excretion -Toia urinary excretion of chloramphenicol ranges from 68% to 99% over 3 days. Most chloramphenicol detected in the blood is in the active free form. The elimination half-life of chloramphenicol is approximately 4 hours. 

Didanosine (Videx) Urinary excretion is also a major route of didanosine elimination in pediatric patients therefore, the clearance of didanosine may be altered in children with renal impairment. Although there are insufficient data to recommend P.1090... 

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