Renal excretion delayed

Schaub et al. demonstrated that Mrp2/MRP2 is expressed in the proximal tubules in the kidney (241,242). In vivo study and clinical study supports that Mrp2/MRP2 is involved in the tubular secretion of organic anions. The urinary excretion rates of calcein and fluo-3 were three to four times lower in perfused kidneys from TR rats compared with normal rats, and the renal excretion of lucifer yellow was delayed in TR rats (243). Hulot et al. identified a heterozygous mutation, which results in a loss of function of MRP2, in the patient who showed delay of renal MTX elimination (244). 

Drugs that alter the pH of urine can significantly affect the renal excretion of other drugs. Acid urine increases the effectiveness of mercurial diuretics. It also accelerates the excretion of basic drugs such as meperidine, tricyclic antidepressants, amphetamines, and antihistamines. Acidic drugs, such as aspirin, streptomycin, phenobarbital, sulfonamides, nalidixic acid, and nitrofurantoin have been shown to increase renal clearance in alkaline urine (61). The possible effects of urine pH on the renal excretion of drugs has been illustrated by the observation that if urine is rendered sufficiently alkaline, the excretion of amphetamine is markedly delayed and effective blood levels, after a single dose, can be maintained for several days (62). 

Renal clearance of drugs is delayed in newborns and young infants, necessitating dose reductions (Figure 23.7), but after 8 to 12 months of age, renal excretion of drugs is comparable with that of older children and may even exceed that of adults. In young... 

Mesalazine. Patients intolerant of salazopyrin usually tolerate mesalazine, which is 5-ASA. Mesalazine is absorbed rapidly and completely in the upper jejunum, and is presented in various formulations which delay its release. Asacol tablets are coated in a resin, which dissolves only at a pH of 7 or higher, favouring its release in the ileum and colon. In contrast Pentasa has a slow-release but pH independent coating so that 5-ASA is liberated throughout the gastrointestinal tract. 5-ASA that enters the blood is rapidly cleared by acetylation in the liver and renal excretion. In addition to oral formulations, mesalazine is available as an enema. 

PHARMACOKINETICS AND PHARMACODYNAMICS Most NSAIDs are rapidly and completely absorbed from the GI tract, with peak concentrations occurring within 1 hours. Aspirin begins to acetylate platelets within minutes of reaching the presystemic circulation. The presence of food tends to delay absorption without affecting peak concentration. Most NSAIDs are extensively protein bound (95-99%) and undergo hepatic metabolism and renal excretion. In general, NSAIDs are not recommended in the setting of advanced hepatic or renal disease due to their adverse pharmacodynamic effects see below). 

Piroxicam (feldene) is approved in the U.S. for the treatment of rheumatoid arthritis and osteoarthritis. Due to delayed attainment of steady state (7-12 days), it has slow onset of action and is less suited for acute analgesia, but has been used in acute gout. Piroxicam can reduce the renal excretion of lithium to a clinically significant extent. The usual daily dose is 20 mg. 

E. Pharmacokinetics. Acetylsalicylic acid is well absorbed from the stomach and small intestine. Large tablet masses and enteric-coated products may dramatically delay absorption (hours to days). The volume of distribution of salicylate is about 0.1-0.3 L/kg, but this can be increased by acidemia, which enhances movement of the drug into cells. Elimination is mostly by hepatic metabolism at therapeutic doses, but renal excretion becomes important with overdose. The elimination half-life is normally 2—4.5 hours but as long as 18-36 hours after overdose. Renal elimination is dependent on urine pH. See also Table 11-59 (p 381). 

I. Pharmacology. Phenobarbital Is a barbiturate commonly used as an anticonvulsant. Because of the delay In onset of the therapeutic effect of phenobarbital, diazepam (see p 415) Is usually the Initial agent for parenteral anticonvulsant therapy. After an oral dose of phenobarbital, peak brain concentrations are achieved within 10-15 hours. Onset of effect after intravenous administration is usually within 5 minutes, although peak effects may take up to 30 minutes. Therapeutic plasma levels are 15-35 mg/L. The dmg is eliminated by metabolism and renal excretion, and the elimination half-life is 48-100 hours. 

One study found that ranitidine 150 mg twice daily for one day reduced the absorption of procainamide from the gut by 10% and reduced its renal excretion by 19%, increasing the procainamide and A-acetylprocainamide AUC by about 14%. However, no change in the steady-state pharmacokinetics of procainamide was found with ranitidine 150 mg twice daily in another study, except that ranitidine delayed the time to maximum plasma concentration (from 1.4 to 2.7 hours). In a further study, ranitidine 150 mg twice daily for 4 days caused no significant changes in the mean pharmacokinetics of oral procainamide 1 g in 13 healthy subjects. However, it appeared that subjects had either a modest 20% increase or decrease in procainamide clearance, with the direction of change related to their baseline procainamide clearance the higher the baseline clearance the greater the decrease caused by ranitidine. ... 

Absorption of nadolol after po dosing is variable, averaging about 30%. The presence of food does not affect absorption. There is no hepatic first-pass metabolism and peak plasma concentrations are achieved in 3—4 h after po doses. About 30% of the plasma concentration is protein bound. The elimination half-hfe of nadolol is 20—24 h, allowing once a day dosing. The dmg is excreted unchanged by the kidneys and its excretion is delayed in patients having renal failure (98,99,108). 

Therapy with leucovorin/5-FU must not be initiated or continued in patients who have symptoms of Gl toxicity of any severity, until those symptoms have completely resolved. Patients with diarrhea must be monitored with particular care until the diarrhea has resolved, as rapid clinical deterioration leading to death can occur. Methotrexate concentrations Monitoring of the serum methotrexate concentration is essential in determining the optimal dose and duration of treatment with leucovorin. Delayed methotrexate excretion may be caused by a third space fluid accumulation, renal insufficiency, or inadequate hydration. Under such circumstances, higher doses of leucovorin or prolonged administration may be indicated. Doses higher than those recommended for oral use must be given IV. 

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... 

Pharmacokinetics Well absorbed from the GI tract (food delays absorption). Protein binding 20%-40%. Widely distributed (including to CSF). Metabolized in the liver to active metabolite. Primarily excreted in urine. Minimal removal by hemodialysis. Half-life 4-6 hr (increased in impaired renal function and the elderly). 

The highly polar ionic character of EDTA limits its oral absorption. Moreover, oral administration may increase lead absorption from the gut. Consequently, EDTA should be administered by intravenous infusion. In patients with normal renal function, EDTA is rapidly excreted by glomerular filtration, with 50% of an injected dose appearing in the urine within 1 hour. EDTA mobilizes lead from soft tissues, causing a marked increase in urinary lead excretion and a corresponding decline in blood lead concentration. In patients with renal insufficiency, excretion of the drug—and its metal-mobilizing effects—may be delayed. 

On the other hand, acidic drugs tend to ionize under conditions of alkaline pH and so are unable to permeate the renal tubular epithelium and are preferentially excreted. Tire converse applies to conditions of acidic urinary pH. This has been demonstrated experimentally for many drugs weak bases are excreted more rapidly in acidic urine, whereas weak acids are excreted more rapidly in alkaline urine. In the horse, phenylbutazone, which is a weak organic acid with a pKa of 4.6, has a more delayed clearance time under conditions of aciduria than under conditions of alkaline urine. 

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