The pharmacokinetics of chloramphenicol in the neonate and young infant

Mulhall, Anne; Louvois, J de; Hurley, Rosalinde

doi:10.1093/jac/12.6.629

Cited by 25 publications

(7 citation statements)

References 2 publications

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“…it may still be considered in certain clinical situations. Intramuscular administration of ch loramphenicol succinate produced even lower serum concentrations than oral administration (Mulhall et al 1983b). The palmitate ester removes the bitter taste of chloramphenicol to allow for oral administration, but it must be hydrolysed to active chloramphenicol in the gastrointestinal tract by pancreatic lipases before absorption can occur.…”

Section: Chloramphenicolmentioning

confidence: 99%

“…and C L in neonates has ranged from 0.022 10 0.23 L/ h/kg, demonstrating a IO-fold variat ion (Mul hall el al. 1983), whi le conflicting reports correlating C L with gestational age have also been published (Glazer et al 1980;Mulhall et al 1983b;Rajchgot et al \983). Several studies have correlated chloramphenicol CL wi th postnatal age (Mulhall et a!.…”

Section: Chloramphenicolmentioning

confidence: 99%

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Clinical Pharmacokinetics of Antibacterial Drugs in Neonates

Paap

Nahata

1990

Clinical Pharmacokinetics

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Neonatal patients are surviving longer due to the rapid advances in medical knowledge and technology. Our understanding of the developmental physiology of both preterm and full term neonates has also increased. It is now apparent that differences in body composition and organ function significantly affect the pharmacokinetics of antibacterial drugs in neonates, and dosage modifications are required to optimise antimicrobial therapy. The penicillins and cephalosporins are frequently used in neonates. Although ampicillin has replaced benzylpenicillin (penicillin G) for empirical treatment of neonatal sepsis, many of the other penicillins may be used in neonates for the management of various infections. Increased volume of distribution (Vd) and decreased total body clearance (CL) affect the disposition of penicillins and cephalosporins. Decreased renal clearance (CLR) due to decreased glomerular filtration and tubular secretion is responsible for the decreased CL for most of the beta-lactams. Aminoglycoside Vd is affected by the increased total body water content and extracellular fluid volume of neonates. The increased Vd, in part, accounts for the extended elimination half-life (t1/2) observed in neonates. Aminoglycoside CL is dependent on renal glomerular filtration which is markedly decreased in neonates, especially those preterm. These drugs appear to be less nephrotoxic and ototoxic in neonates than in older patients, and the role of serum concentration monitoring should be limited to specific neonatal patients. Other antibiotics such as vancomycin, teicoplanin, chloramphenicol, rifampicin, erythromycin, clindamycin, metronidazole and cotrimoxazole (trimethoprim plus sulfamethoxazole) may be used in certain clinical situations. The emergence of staphylococcal resistance to penicillins has increased the need for vancomycin. With the exceptions of vancomycin and chloramphenicol, the efficacy and safety of these other agents in neonates have not been established. The need for serum vancomycin concentration monitoring may be limited, as with aminoglycosides, while safety concerns warrant the routine monitoring of serum chloramphenicol concentrations in neonates. Dosing guidelines are provided, based on the pharmacokinetics of the drugs and previously published recommendations. These dosing guidelines are intended for initial therapy, and close therapeutic monitoring is recommended for maintenance dose requirements to optimise patient outcome. There has been an enormous increase in our knowledge of neonatal physiology and drug disposition. Fortunately, many of the antibacterial drugs used in neonates (e.g. penicillins and cephalosporins) are relatively safe. It will be important to evaluate all newly developed antibiotics in neonates to assure their maximum efficacy and safety.

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Section: Chloramphenicolmentioning

confidence: 99%

Section: Chloramphenicolmentioning

confidence: 99%

Clinical Pharmacokinetics of Antibacterial Drugs in Neonates

Paap

Nahata

1990

Clinical Pharmacokinetics

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“…5,6 Therapeutic plasma concentrations of chloramphenicol are considered to range from a trough of 5-10 mg/L to a peak of 10-20 mg/L. 23,24 The majority of our patients treated initially by im injection were well below these values during the first 8 h of the study. Institution of oral therapy after this time and its greater bioavailability resulted in satisfactory plasma chloramphenicol concentrations the next day regardless of initial route of parenteral administration.…”

Section: Discussionmentioning

confidence: 91%

Factors affecting the pharmacokinetics of parenteral chloramphenicol in enteric fever

Acharya

Davis²,

Ho³

et al. 1997

Journal of Antimicrobial Chemotherapy

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Chloramphenicol pharmacokinetics were studied in 29 Nepalese adults diagnosed with uncomplicated enteric fever and randomized to receive succinate ester 30 mg/kg i.v. or i.m. Serial plasma concentrations of chloramphenicol, and iothalamate (to estimate glomerular filtration rate), antipyrine (hepatocellular function) and Indocyanine Green (liver blood flow) were measured by HPLC and kinetic parameters estimated by non-compartmental analysis. In culture-positive patients (n = 16), mean residence times (MRTs) and steady-state volumes of distribution (V(d)ss) for i.v. chloramphenicol (mean +/- S.D.; 4.9 +/- 0.9 h and 1.9 +/- 0.8 L/kg; n = 7) were less than after i.m. chloramphenicol (12.3 +/- 7.3 h and 3.7 +/- 2.5 L/kg; n = 9; P < 0.05), with a higher peak plasma concentration after i.v. (16.2 +/- 9.1 versus 7.8 +/- 3.6 mg/L; P < 0.05); plasma clearance (Cl(p)) was similar in the two groups (368 +/- 172 and 310 +/- 224 mL/kg/min after i.v. and i.m. respectively). In 17 patients examined during convalescence, MRT and Vdss were less than in acute illness regardless of route chloramphenicol administration. There were similar changes in chloramphenicol kinetic parameters in culture-negative patients. Antipyrine Cl(p) and liver blood flow correlated weakly with chloramphenicol Cl(p) in culture-positive patients (P < 0.1) and were higher in convalescence; no such associations were seen for iothalamate Cl(p). These data indicate that i.v. chloramphenicol produces peak plasma concentrations which are on average twice those after i.m. injection of the same dose, due principally to a smaller V(d)ss. Cl(p) is uninfluenced by route of administration and is determined more by hepatic metabolism than renal excretion. Intramuscular treatment may result in sub-therapeutic chloramphenicol concentrations initially, but continued regular i.v. dosing is more likely to produce levels at which bone marrow toxicity occurs.

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“…Neonates have long been a vulnerable population to unstudied therapies, starting as early as the late nineteenth century with Mrs. Winslow’s Soothing Syrup, a purported remedy for teething that contained alcohol and morphine sulfate, causing numerous infant deaths ( 1 ). In 1959, Gray baby syndrome was first reported in infants receiving large doses of chloramphenicol as a broad spectrum antibacterial agent ( 2 ), and in 1983, Mulhall et al ( 3 ) noted the altered pharmacokinetics (PK) of chloramphenicol in neonates and young infants resulting in elevated serum levels and some toxic effects.…”

mentioning

confidence: 99%

“…There are a number of examples of altered PK for drugs used in neonates including chloramphenicol ( 3 ), gentamicin ( 12 ), and most recently clindamycin ( 13 ). Drug elimination may even be faster in small preterm neonates and the dose requirement may be as much as triple that of the adults as seen in the publication on micafungin ( 14 ).…”

mentioning

confidence: 99%