Erythromycin elimination

The complete degradation of sulfamethoxazole was also reported within 14 days with P. chrysosporium, Bjerkandera sp. R1 and B. adusta [4], although, contrary to the reports of enzymatic transformation, metabolites were not identified. Partial removal (from 30% to 55%) of sulfamethoxazole from activated-sludge-mixed liquor and the effluent of a WWTP was demonstrated at bench scale within 5 days with P. chrysosporium propagules entrapped in a granular bioplastic formulation [25]. This approach was also successful in the partial elimination of other kinds of antibiotics, eg., ciprofloxacin (see below) and the macrolide erythromycin. 

Coagulation/flocculation/precipitation of HWWs by means of FeCl3 or Al2(S04)3 seems to be a suitable option for removing lipophilic compounds, such as diclofenac, although it is unable to eliminate many other common hydrophilic PhCs, including carbamazepine, iopromide, diazepam and antibiotics (i.e. roxy-thromycin, erythromycin, trimethoprim), from the liquid phase [66]. 

Drugs that interfere with biliary excretion of glucuronidation (erythromycin, rifampin, cholestyramine) might decrease entacapone elimination. 

The macrolides are orally absorbed but they are acid-labile. They therefore need to be administered in acid-resistant capsules or as acid-resistant esters. The macrolides are widely distributed into all fluids except the CNS. Protein binding is about 90%. They are eliminated via biliary excretion with extensive enterohepatic circulation. Elimination half-lives vary from 1.4 h for erythromycin to 40-60 h for azithromycin. 

Roxithromycin, clarithromycin, azithromycin and dirithromycin are more recently developed macrolides with similar antimicrobial activity to erythromycin. However they are better absorbed, have longer elimination half-lives and lower incidence of gastrointestinal side-effects. Azithromycin and... 

The taxanes are practically insoluble in water and solubility is limited to mixtures of ethanol with poly-ethoxylated castor oil. They are generally administered in 3-24 hour infusions. The taxanes are for 90-95% plasma protein bound and primarily metabolized by P450 enzymes in the liver. Less than 10% is excreted in the urine as parent compounds. The elimination half-life of docetaxel is approximately 10 hours while that of paclitaxel has been vary-ingly reported between 5 and 50 hours. Inhibitors of the cytochrome P450 isoenzyme Cyp3A4, like keto-conazole and erythromycine, are contraindicated. 

Erythromycin and azithromycin are excreted primarily in active form in bile, with only low levels found in urine. Clarithromycin is metabolized to the biologically active 14-OH metabolite and is eliminated largely by the kidney. The half-life of erythromycin is approximately 1.4 hours, whereas the half-life of clarithromycin is 3 to 7 hours and that of azithromycin approaches 68 hours. 

By definition, the fraction that enters the circulatory system is eliminated by extrarenal mechanisms (usually metabolism by the liver and other tissues) and is derived by the difference from renal excretion that is, 1 — Fg. The excretory organs are able to eliminate polar compounds such as tetracycline and tylosin more efficiently than compounds that are highly soluble in lipids (i.e., lipophilic) such as metronidazole, erythromycin, clindamycin, and trimethoporin. Thus, the highly lipophilic compounds will not be eliminated until they are metabolized to more polar intermediates. 

The biotransformation of the phenylpiperidines is primarily by hepatic phase I metabolism, catalysed by cytochrome P-450 isoenzymes. The elimination of alfentanil is significantly slowed in patients treated with erythromycin, a P-450 inhibitor, with delayed recovery and prolonged postoperative respiratory depression (Bartkowski and McDonnell 1990). Apart from pethidine and phenoperidine, none of the phenylpiperidines has pharmacologically active metabolites. 

Buspirone is rapidly absorbed orally but undergoes extensive first-pass metabolism via hydroxylation and dealkylation reactions to form several active metabolites. The major metabolite is l-(2-pyrimidyl)-piperazine (1-PP), which has K2-adrenoceptor-blocking actions and which enters the central nervous system to reach higher levels than the parent drug. It is not known what role (if any) 1-PP plays in the central actions of buspirone. The elimination half-life of buspirone is 2-4 hours, and liver dysfunction may slow its clearance. Rifampin, an inducer of cytochrome P450, decreases the half-life of buspirone inhibitors of CYP3A4 (eg, erythromycin, ketoconazole, grapefruit juice, nefazodone) can markedly increase its plasma levels. 

Clarithromycin is metabolized in the liver. The major metabolite is 14-hydroxyclarithromycin, which also has antibacterial activity. A portion of active drug and this major metabolite is eliminated in the urine, and dosage reduction (eg, a 500-mg loading dose, then 250 mg once or twice daily) is recommended for patients with creatinine clearances less than 30 mL/min. Clarithromycin has drug interactions similar to those described for erythromycin. 

Erythromycin distributes widely in the body with residue levels in tissues generally exceeding those in serum. Both hepatic and renal routes of elimination of erythromycin are significant and it undergoes enterohepatic circulation. Elimination of erythromycin in relatively high levels in the feces may follow its oral administration. As with almost all macrolides, the principal metabolic pathway of erythromycin is by A-desmethylation of the desosamine sugar (107). 

Hepatic dysfunction Antibiotics that are concentrated or eliminated by the liver (for example, erythromycin, tetracycline) are contraindicated in treating patients with liver disease. 

Excretion Erythromycin and azithromycin are primarily concentrated and excreted in an active form in the bile. Partial reabsorption occurs through the enterohepatic circulation. In contrast, clarithromycin and its metabolites are eliminated by the kidney as well as the liver and it is recommended that dosage be adjusted in patients with compromised renal function. 

Interactions Erythromycin and clarithromycin inhibit the hepatic metabolism of theophylline, warfarin, terfenadine, astemizole, carbamazepine and cyclosporine which can lead to toxic accumulations of these drugs. An interaction with digoxin may occur in some patients. In this case, the antibiotic eliminates a species of intestinal flora that ordinarily inactivates digoxin, thus leading to greater reabsorption of digoxin from the enterohepatic circulation. 

Absorption after oral administration is best with erythromycin estolate, even if there is food in the stomach. Hydrolysis of the estolate in the body releases the active er5dhromycin which diffuses readily into most tissues the t) is dose-dependent cind elimination is cJmost exclusively in the bile and faeces. 

In gastroenteritis caused by Campylobacter jejuni, erythromycin is effective in eliminating the organism from the faeces, although it does not reduce the duration of the symptoms unless given very early in the course of the illness. 

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