Kinetic disposition of intravenous ceftriaxone in normal subjects and patients with renal failure on hemodialysis or peritoneal dialysis

Ti, Teow-Yee; Fortin, Louis-Jacques; Kreeft, John H.; East, Donald S.; Ogilvie, Raymond; Somerville, Peter J.

doi:10.1128/aac.25.1.83

Cited by 48 publications

(15 citation statements)

References 10 publications

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“…When compared with normal volunteers or pa tients with mild to moderate renal func tion impairment the Clp was significantly reduced. These results are in agreement with those previously reported [1,6,7,15]. Our findings cannot be compared with those of Stoeckel et al [13] since we did not measure free plasma ceftriaxone levels and therefore we do not know its influence over the nonrenal ceftriaxone Clp in our patients.…”

Section: Discussionsupporting

confidence: 90%

“…The finding that Clp was lower than Clf during hemodialy sis may reflect either an overestimation of the Clf by overestimating the blood flow or some degree of recirculation in the arterio venous fistula despite the fact that all pa tients were dialyzed with two needles. Our results contrast with previous reports [6,7,11] but they are in agreement with those of Ti et al [15] who found a significant dialyzer clearance similar to the Clf reported in our study, but they could not find a significant Clp increase. The most likely explanation for this contradictory find ings is recirculation in the arteriovenous fistula since one-needle hemodialysis was used in most of their patients.…”

Section: Discussionsupporting

confidence: 78%

“…They are frequent ly exposed to several bacterial pathogens and are very likely to develop life-threat ening infections [3]. The aminoglycosides had been a very useful tool in their treat ment, however, the narrow range between toxic and therapeutic blood levels stim ulated the search for new, less toxic antibiotics capable of successfully replac ing them [1,15].…”

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confidence: 99%

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Single-Dose Pharmacokinetics of Ceftriaxone in Patients with End-Stage Renal Disease and Hemodialysis

Garcia¹,

Santivanez²,

Battilana³

1988

Chemotherapy

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We report the pharmacokinetic parameters of ceftriaxone in 11 patients on hemodialysis with end-stage renal disease (ESRD; creatinine clearance < 5 ml/ min/1.73 m²). The patients were studied during the interdialysis period and during 4h of hemodialysis. The mean age was 53.4 years. After the administration of 1 g of ceftriazone during a constant intravenous infusion over a 30-min period, t_½ was 16.6 h, β was 0.0418 ± 0.0106 h^-1, V_D was 14.5 ± 3.0 liters/1.73 m² and Cl_p was 0.40 ± 0.05 liters/h for the interdialysis period. Hemodialysis started 24 h after the infusion. The initial plasma ceftriaxone concentration was 68.6 ± 10.8 μg/ml. This value dropped to 40.4 ± 4.7 μg/ml at the end of the 4th hour, indicating a significant 41% decay in blood levels during hemodialysis (p < 0.001). The t_½ decreased to 4.88 h, k_el rose to 0.142 ± 0.0250 h^-1 and Cl_p increased to 1.73 ± 0.44 liters/h. All values were highly significantly different (p < 0.001) from those during the interdialysis period. The plasma ceftriaxone concentration of 40.4 ± 4.7 μg/ml at the end of hemodialysis was well within the therapeutic range of the drug. We conclude that ceftriaxone has a moderated increase in t_½ in patients with ESRD. Ceftriaxone is significantly dialyz-able, however, the plasma concentrations are in the therapeutic range by the end of a 4-hour hemodialysis, 28 h after the administration of the drug. We propose that 1 g given intravenously before each hemodialysis will be sufficient to keep the patient’s plasma concentrations within the therapeutic range until the next hemodialysis. If the interdialysis period is longer than 48 h an extra dose should be administered.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 78%

mentioning

confidence: 99%

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Single-Dose Pharmacokinetics of Ceftriaxone in Patients with End-Stage Renal Disease and Hemodialysis

Garcia¹,

Santivanez²,

Battilana³

1988

Chemotherapy

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“…The reason of this slow elimination of ceftriaxone is related to its side chain in position 3 and its high protein binding of 95% which decreases the glomerular filtration rate and limits its hepatic clearance, only the unbound frac tion being eliminated [13]. Similar results were found by others [11,14,15].…”

Section: Serum Pharmacokinetics Inhibitory Quotientsupporting

confidence: 71%

Pharmacokinetics of Ceftriaxone and Its Relation to Concentrations in Extravascular Compartments

Regamey¹

1985

Chemotherapy

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Two of the 3rd generation cephalosporins, ceftriaxone and cefotaxime, have an almost identical antibacterial spectrum, but completely different pharmacokinetics. After an intravenous dose of 1 g, peak levels of both cephalosporins were > 100 μg/ml. Cefotaxime levels fall rapidly with a T½ of 1.1 h, whereas ceftriaxone persists for 24 h with an unique T½ of 8 h. Cefotaxime is eliminated by the kidneys and metabolized to desacetyl-cefotaxime resulting in a high total clearance. In contrast, ceftriaxone is not metabolized and highly protein bound with a total clearance of only 14 ml/min. Peak concentrations of antibiotics are lower in extravascular compartments than in serum. They depend on the dose administered and the serum T½; they are lower with highly bound drugs. Concentrations of ceftriaxone and cefotaxime were measured by Andrews and Wise in blister fluids, in ascites and pleural fluid by us. We found concentrations of 20–26 μg/ml ceftriaxone up to 12 h in ascites, but only 7–15 μg/ml cefotaxime. The levels persisted for 24 h for ceftriaxone, whereas they fell rapidly for cefotaxime. Because the minimum inhibition concentrations increase in the presence of proteins, and because free, unbound, microbiologically active ceftriaxone is lower than the measured total antibiotic concentrations, we suggest that 2-gram doses should be administered – at least at the beginning of the treatment of an infectious disease – and for prophylaxis.

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“…Its major route of elimination is via the kidney (41-60%), wherein it is disposed by glomerular filtration without any significant renal tubular secretion [15,16,22]; the remainder is excreted in the bile [15,16]. In ESRD patients the T ½ of the drug has been reported to be much longer but variable, ranging from 11.7 to 17.3 h [19,23,24]. It has been shown that ceftriaxone is not removed to any significant extent from plasma by hemodialysis [19,20].…”

Section: Discussionmentioning

confidence: 99%

Ceftriaxone Is an Efficient Component of Antimicrobial Regimens in the Prevention and Initial Management of Infections in End-Stage Renal Disease

2000

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Background: Infection is a frequent complication in patients with end-stage renal disease. The most common organisms isolated are gram-positive cocci and gram-negative bacilli. Therefore, the usual initial therapeutic approach in these situations is the simultaneous intravenous administration of vancomycin plus an aminoglycoside. This treatment's adverse effects include ototoxicity, nephrotoxicity, and less than ideal tissue penetrance. Methods: We assessed the efficacy of intravenous ceftriaxone in the prevention and in the initial empirical treatment of infections in end-stage renal disease patients, and tested the stability of blood levels of this antibiotic in this population. We studied 104 patients, 65 of them falling into the prevention group (1 g of ceftriaxone i.v. for 5 days) and 39 into the treatment group (1 g of ceftriaxone i.v. or intraperitoneally for 10-14 days). Results: Peak serum ceftriaxone concentrations were well above the minimal inhibitory concentration for 90% of strains. Trough serum concentrations of the drug prior to the next dose were also considerably in excess of the minimal inhibitory concentration. In the prevention group, 8 of 65 developed an infection, which was sensitive to ceftriaxone, whereas in 22 of the 39 patients from the treatment group, cultures showed organisms sensitive to ceftriaxone and in the remaining 17 patients sensitivity was not done. Conclusions: The present study demonstrates the efficacy of a simplified dosing schedule in achieving blood levels of the antibiotic well in excess of minimal inhibitory concentration of any of the organisms encountered. It also shows the usefulness of ceftriaxone in the prevention and/or treatment of bacterial infections and the lack of the side effects vancomycin and/or aminoglycosides possess.

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Kinetic disposition of intravenous ceftriaxone in normal subjects and patients with renal failure on hemodialysis or peritoneal dialysis

Cited by 48 publications

References 10 publications

Single-Dose Pharmacokinetics of Ceftriaxone in Patients with End-Stage Renal Disease and Hemodialysis

Single-Dose Pharmacokinetics of Ceftriaxone in Patients with End-Stage Renal Disease and Hemodialysis

Pharmacokinetics of Ceftriaxone and Its Relation to Concentrations in Extravascular Compartments

Ceftriaxone Is an Efficient Component of Antimicrobial Regimens in the Prevention and Initial Management of Infections in End-Stage Renal Disease

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