Mezlocillin pharmacokinetics in pediatric oncology patients

Kramer, William G.; Pickering, L K; Culbert, Steven J.; Frankel, Lawrence S.

doi:10.1128/aac.25.1.62

Cited by 3 publications

(3 citation statements)

References 9 publications

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“…Therefore, nafcillin can be administered to older children at the same dosage intervals as those used in adult patients. Kramer et al (1984) Abbreviations: CF = cystic fibrosis; CL = total body clearance; Cmax= maximal serum concentration; qid = 4 times daily; qxh = every x hours; l1,11~ = elimination half-life; Vd = volume of distribution.…”

Section: Nafcillinmentioning

confidence: 99%

Pharmacokinetics of Anti-Infective Agents in Paediatric Patients

Butler

Kuhn

Chandler

1994

Clinical Pharmacokinetics

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Various differences in drug disposition exist between children and adults. For example, the volume of distribution (Vd) for many drugs is larger in children than in adults. Other parameters, including excretion and elimination may be altered in children compared with adults. The penicillins and cephalosporins are used commonly for the treatment of infection in paediatric patients. The increased Vd in children contributes to the increased elimination half-life of these agents. Clearance of the acylureido-penicillins is increased in children with cystic fibrosis, a disease that decreases the elimination half-life for these drugs. Aminoglycosides distribute into extracellular fluid and their pharmacokinetic profile is affected by changes in Vd. The Vd for aminoglycosides is slightly higher in children than in adults. Children with cystic fibrosis, burns, or cancer have higher clearance rates and larger Vd values for aminoglycosides. Few data in the literature address the pharmacokinetics of other anti-infective agents, including vancomycin, teicoplanin, erythromycin, metronidazole, chloramphenicol, and cotrimoxazole (trimethoprim-sulfamethoxazole), in children. Similarly, there is little information regarding the pharmacokinetic profile of antivirals and antifungals in children. Dosage guidelines are available to enable the clinician to initiate anti-infective therapy in children. Subsequent dosage requirements may change based on the patient's current clinical condition. Although several studies have investigated the pharmacokinetics of anti-infectives in neonates and adults, data for children are limited. Therefore, further studies are required so that the ever growing arsenal of anti-infectives can be administered appropriately to children.

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Section: Nafcillinmentioning

confidence: 99%

Pharmacokinetics of Anti-Infective Agents in Paediatric Patients

Butler

Kuhn

Chandler

1994

Clinical Pharmacokinetics

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“…The pharmacokinetics of mezlocillin must be understood to design dosage regimens which provide drug concentrations in serum above the MIC for the target organism. In addition, it may be important in some instances to determine the mezlocillin concentration at or near the site of infection, for example, in urine or cerebrospinal fluid (1,2,7,8).High-pressure liquid chromatographic (HPLC) assays are frequently used for pharmacokinetic studies of antibiotics because of their specificity, sensitivity, speed, and range of linearity. A number of HPLC methods for determination of mezlocillin levels have been described previously (3)(4)(5)(6).…”

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Improved micromethod for mezlocillin quantitation in serum and urine by high-pressure liquid chromatography

Fiore¹,

Auger²,

Drusano³

et al. 1984

Antimicrob Agents Chemother

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A rapid, sensitive, and specific method of analysis for mezlocillin in serum and urine by high-pressure liquid chromatography is described. A solid-phase extraction column was used to remove interfering substances from samples before chromatography. Quantitation included the use of an internal standard, nafcillin. Mezlocillin was chromatographed with a phosphate buffer-acetonitrile (73:27) mobile phase and a C-18 reverse-phase column and detected at a wavelength of 220 nm. The assay had a sensitivity of 1.6 ,ug/ml and a linearity of up to 600 ,ug/ml and 16 mg/ml in serum and urine, respectively, with only 0.1 ml of sample. The interday and intraday coefficients of variation for replicate analyses of spiked serum and urine specimens were less than 6.5%.Mezlocillin is a relatively new member of the ureidopenicillin class of antibiotics. It possesses a broader spectrum of activity against aerobic and anaerobic bacteria than the older semisynthetic penicillins. The pharmacokinetics of mezlocillin must be understood to design dosage regimens which provide drug concentrations in serum above the MIC for the target organism. In addition, it may be important in some instances to determine the mezlocillin concentration at or near the site of infection, for example, in urine or cerebrospinal fluid (1,2,7,8).High-pressure liquid chromatographic (HPLC) assays are frequently used for pharmacokinetic studies of antibiotics because of their specificity, sensitivity, speed, and range of linearity. A number of HPLC methods for determination of mezlocillin levels have been described previously (3)(4)(5)(6). One method requires a time-consuming extraction step and results in poor recovery (<50%) of mezlocillin (4). The other two HPLC procedures (3,6) are relatively simple, sensitive, and specific for mezlocillin in serum or plasma; however, they require a sample volume of at least 0.5 ml, and none of these methods use an internal standard.The objective of this study was to develop a more rapid, specific, and sensitive HPLC assay for the measurement of mezlocillin in serum and urine with an internal standard and small sample volumes (0.1 ml).HPLC The buffer solution used throughout the study was 0.07 M potassium dihydrogen phosphate adjusted to pH 5.0 with 5 M sodium hydroxide. Nafcillin, the internal standard, was prepared at a concentration of 190 Fig/ml in buffer and frozen in 1-ml portions in disposable polypropylene tubes (Bio-Rad Laboratories, Richmond, Calif.). Serum standards for mezlocillin were prepared from a stock solution of 6,040 ,ug/ml in blank serum to contain 6, 12, 48, 97, 242, 423, or 604 p.g of mezlocillin per ml. Urine standards were prepared from a * Corresponding author. stock solution of 73 mg/ml to contain 0.5, 1.0, 3.0, 6.0, 9.2, or 16.2 mg of mezlocillin per ml. Portions of the serum (0.25 ml) and urine (0.25 ml after 1:10 dilution with buffer) standards were stored at -25°C in polypropylene tubes, where they were stable for at least 3 weeks.A volume of 0.10 ml of serum or urine (after 1:10 dilution with ...

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Commonly Used Antibacterial and Antifungal Agents for Hospitalised Paediatric Patients

et al. 2001

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Due to normal growth and development, hospitalised paediatric patients with infection require unique consideration of immune function and drug disposition. Specifically, antibacterial and antifungal pharmacokinetics are influenced by volume of distribution, drug binding and elimination, which are a reflection of changing extracellular fluid volume, quantity and quality of plasma proteins, and renal and hepatic function. However, there is a paucity of data in paediatric patients addressing these issues and many empiric treatment practices are based on adult data. The penicillins and cephalosporins continue to be a mainstay of therapy because of their broad spectrum of activity, clinical efficacy and favourable tolerability profile. These antibacterials rapidly reach peak serum concentrations and readily diffuse into body tissues. Good penetration into the cerebrospinal fluid (CSF) has made the third-generation cephalosporins the agents of choice for the treatment of bacterial meningitis. These drugs are excreted primarily by the kidney. The carbapenems are broad-spectrum beta-lactam antibacterials which can potentially replace combination regimens. Vancomycin is a glycopeptide antibacterial with gram-positive activity useful for the treatment of resistant infections, or for those patients allergic to penicillins and cephalosporins. Volume of distribution is affected by age, gender, and bodyweight. It diffuses well across serous membranes and inflamed meninges. Vancomycin is excreted by the kidneys and is not removed by dialysis. The aminoglycosides continue to serve a useful role in the treatment of gram-negative, enterococcal and mycobacterial infections. Their volume of distribution approximates extracellular space. These drugs are also excreted renally and are removed by haemodialysis. Passage across the blood-brain barrier is poor, even in the face of meningeal inflammation. Low pH found in abscess conditions impairs function. Toxicity needs to be considered. Macrolide antibacterials are frequently used in the treatment of respiratory infections. Parenteral erythromycin can cause phlebitis, which limits its use. Parenteral azithromycin is better tolerated but paediatric pharmacokinetic data are lacking. Clindamycin is frequently used when anaerobic infections are suspected. Good oral absorption makes it a good choice for step-down therapy in intra-abdominal and skeletal infections. The use of quinolones in paediatrics has been restricted and most information available is in cystic fibrosis patients. High oral bioavailability is also important for step-down therapy. Amphotericin B has been the cornerstone of antifungal treatment in hospitalised patients. Its metabolism is poorly understood. The half-life increases with time and can be as long as 15 days after prolonged therapy. Oral absorption is poor. The azole antifungals are being used increasingly. Fluconazole is well tolerated, with high bioavailability and good penetration into the CSF. Itraconazole has greater activity against aspergillus, blastomycosis,...

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Mezlocillin pharmacokinetics in pediatric oncology patients

Abstract: The pharmacokinetics of mezlocillin were studied in 31 children (age, 2

Cited by 3 publications

References 9 publications

Pharmacokinetics of Anti-Infective Agents in Paediatric Patients

Pharmacokinetics of Anti-Infective Agents in Paediatric Patients

Improved micromethod for mezlocillin quantitation in serum and urine by high-pressure liquid chromatography

Commonly Used Antibacterial and Antifungal Agents for Hospitalised Paediatric Patients

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