Chloramphenicol clearance

After intravenous dosing, chloramphenicol clearance in ruminant species is rapid and the terminal half-life is short ... 

The seeond study demonstrated a different interaetion, in that the elear-ance of chloramphenicol was increased and the half-life reduced This study has also been criticised as it does not account for the fact that chloramphenicol clearance increases over the duration of a treatment course, which suggests that the changes seen in the pharmacokinetics of chloramphenicol may be independent of the paracetamol. The authors later admit this as a possibility. The third study found no differences in the pharmacokinetics of chloramphenicol after the first dose, but at steady state, the AUC and peak serum levels of chloramphenicol were lower in children who also received paracetamol. ... 

The activity of glucuronidation is low in the newborn, especially in premature babies (6). This is evident in the jaundice observed in many newborns because the major clearance pathway for bilirubin is glucuronidation. This can also lead to increased toxicity of some drugs in the newborn such as the grey baby syndrome seen in newborns treated with chloramphenicol. 

Chloramphenicol Serum iron levels may be increased because of decreased iron clearance and erythropoiesis due to direct bone marrow toxicity from chloramphenicol. 

Chloramphenicol Prevents bacterial protein synthesis by binding to the 50S ribosomal subunit Bacteriostatic activity against susceptible bacteria Use is rare in the developed world because of serious toxicities Oral, IV hepatic clearance (half-life 2.5 h) dosage is 50-100 mg/kg/d in four divided doses Toxicity Dose-related anemia, idiosyncratic aplastic anemia, gray baby syndrome... 

TACROLIMUS CHLORAMPHENICOL Toxic blood levels of tacrolimus, usually on the second day of starting chloramphenicol Attributed to impaired clearance of tacrolimus by chloramphenicol. Dose i of nearly 80% of tacrolimus may be required to prevent toxicity. Watch for adverse effects. Monitor tacrolimus plasma concentrations... 

These include mesalazine, metformin, NSAIDs, tetracyclines (except doxycycline and minocycline), chloramphenicol, lithium, methotrexate, chloroquine, fibrates, chlorpropamide and glibenclamide, Clinically, it is useful to measure urine output per hour or per 24 hours as a fall in urine output in the presence of adequate fluid intake often indicates or warns of some impairment of renal function. Furthermore, it is neither expensive nor time-consuming to perform a quick test for albumin, casts and red cells in the urine, and to measure pH. Creatinine clearance values are often used to determine the safe doses for several drugs (e.g. NSAIDs, ciclosporin). 

Impaired kidney function, with reduced clearance of chloramphenicol, may be a risk factor for toxicity. 

In a retrospective study of 30 consecutive children with sepsis treated with oral chloramphenicol, weight, albumin, and white blood cell count were the most important determinants for chloramphenicol distribution volume, whereas age, white blood cell count, and serum creatinine were most important for drug clearance (64). A preexisting blood dyscrasia is generally considered to be an absolute contraindication to the use of chloramphenicol. 

In contrast, in five children aged 2.5-5 years paracetamol 50 mg/kg/day for several days significantly lowered the Cmax of chloramphenicol, increased its apparent volume of distribution and clearance, and slightly shortened its half-life (73). 

Inhibition of tacrolimus clearance has been observed in an adolescent renal transplant recipient who was treated with standard doses of chloramphenicol for vancomycin-resistant enterococci. Toxic concentrations of tacrolimus were observed on the second day of chloramphenicol treatment, requiring an 83% reduction in the dose of tacrolimus (81). 

Chloramphenicol is rapidly absorbed in the gastrointestinal tract. Peak serum concentrations occur 1 to 2 hours after the oral dose. In plasma, chloramphenicol is approximately 50% protein bound and is cleared with a half-life of 2 to 3 hours. Peak serum concentrations after administration of chloramphenicol palmitate or succinate occur 4 to 6 hours after the dose. Chloramphenicol distributes to aU tissues, and it concentrates in the cerebrospinal fluid. The drug is actively metabolized by the liver by NATl and UGT. Thus chloramphenicol accumulates in cases of hepatic disease. Renal disease does not dramatically reduce clearance. 

CHLORO- mycehn) Is absorbed rapidly from the GI tract. For intravenous or intramuscular use, chloramphenicol succinate is a prodrug that is hydrolyzed by esterases to chloramphenicol in vivo. Chloramphenicol succinate is rapidly cleared from plasma by the kidneys this may reduce bioavaB-ability, since up to 30% of the dose may be excreted before hydrolysis. Poor renal fimction in the neonate and other states of renal insufficiency result in increased plasma concentrations of chloramphenicol succinate. Decreased esterase activity has been observed in the plasma of neonates and infants, prolonging time to peak concentrations of active chloramphenicol (up to 4 hours) and extending the period over which renal clearance of chloramphenicol succinate can occur. 

Hepatic metabolism to the inactive glucuronide is the major route of elimination. This metabolite and chloramphenicol are excreted in the urine. Patients with impaired liver function have decreased metabolic clearance, and dose should be decreased. About 50% of chloramphenicol is bound to plasma proteins this is reduced in cirrhotic patients and in neonates. Half-life is not altered significantly by renal insufficiency or hemodialysis, and dose adjustment usually is not required. However, if the dose of chloramphenicol has been reduced because of cirrhosis, clearance by hemodialysis may be significant. Drug administration after hemodialysis minimizes this effect. Variabihty in the metabolism and pharmacokinetics of chloramphenicol in neonates, infants, and children necessitates monitoring of plasma drug levels. 

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