Clinical Pharmacokinetics of Ceftriaxone

Yuk, Jae H.; Nightingale, Charles H.; Quintiliani, Richard

doi:10.2165/00003088-198917040-00002

Cited by 63 publications

(36 citation statements)

References 111 publications

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“…The nonlinearity mentioned above has been found at the tissue level (15). It appears that the obstacle put up by a tissue to the penetration of xenobiotic compounds is overcome starting from a certain concentration gradient, and this occurs all the more easily when the gradient is higher (31). Thus, because cephalosporins are antibiotics with a time-dependent immediate effect, the use (in the most serious types of disease) of high doses of CTX (on the order of 2 g) could theoretically favor high peak concentrations in tissue that could increase the diffusible free fraction (3,8,12,13,16,21).…”

Section: Discussionmentioning

confidence: 98%

“…This dosage schedule, which is unusual for a beta-lactam antibiotic, has been validated by a number of clinical studies since CTX came onto the market (11,31). A pharmacodynamic and bacteriological approach taken together with the specific pharmacokinetics of the compound have formed the theoretical basis of a simplified administration schedule compared with those for other beta-lactams with shorter half-lives (9).…”

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Pharmacokinetics and protein binding of ceftriaxone during pregnancy

Bourget

Fernandez

Quinquis

et al. 1993

Antimicrob Agents Chemother

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The purpose of the present work was to study the pharmacokinetics and the protein binding (free fraction of the drug) of ceftriaxone (CTX) during pregnancy. Nine pregnant women (ages, 20 to 34 years) whose gestational ages ranged from 28 4/7 to 40 5/7 weeks were included. The diagnosis of infection was established in all cases; i.e., four women had chorioamnionitis and five women had pyelonephritis. The following triple antibiotic therapy was infused with the aim of achieving cure: CTX, 2 g once every 24 h (constant rate over 60 min); tobramycin, 3 mg/kg of body weight once every 24 h; and ornidazole, 1 g/day. Two series of blood samples were collected, i.e., during the first day of treatment (on day 1), to establish the primary pharmacokinetic profile of CTX, and at the plateau (on day 7), to evaluate a possible accumulation of the drug.This was an open, noncompartmental study, with each patient serving as her own control. Concentrations of total and unbound CTX in serum were measured by a high-performance liquid chromatographic method. Pharmacokinetic analysis was done by a noncompartmental method. Data were compared by a Wilcoxon t test (a P value of .0.05 was considered significant). Data were also compared with those obtained for healthy subjects who received similar treatments. (i) The tolerance to treatment was excellent, and in all cases patients had a complete remission without premature delivery. (ii) No accumulation of CTX was noted during the treatment, and the profiles of the drug determined at days 1 and 7 were not significantly different. (iii) The pharmacokinetic parameters measured in pregnant patients during the third trimester of pregnancy were similar to those measured in healthy subjects. (iv) Residual concentrations of total and unbound CTX measured at 24 h were greater than the MICs for allegedly susceptible organisms, both on day 1 and at steady state. (v) During the final 3 months of pregnancy, the dosage schedule of CTX (2-g infusion per day) required no particular adjustment (i.e., neither a loading dose nor any increase in the maintenance dose).Ceftriaxone (CTX) is the first broad-spectrum cephalosporin prescribed on a single-daily-administration basis (24). This dosage schedule, which is unusual for a beta-lactam antibiotic, has been validated by a number of clinical studies since CTX came onto the market (11, 31). A pharmacodynamic and bacteriological approach taken together with the specific pharmacokinetics of the compound have formed the theoretical basis of a simplified administration schedule compared with those for other beta-lactams with shorter half-lives (9). The dosage recommended by the manufacturer (a single injection of 1 to 2 g every 24 h) is the consequence of an essential peculiarity of CTX: its prolonged terminal half-life (between 6.5 and 8.5 h) (21). The antibacterial spectrum of CTX is similar to that of other broad-spectrum cephalosporins. However, in comparison with other members of the group, it is less active against anaerobic organisms such as Bacteroides fr...

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Pharmacokinetics and protein binding of ceftriaxone during pregnancy

Bourget

Fernandez

Quinquis

et al. 1993

Antimicrob Agents Chemother

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“…que os adultos 9 . O tema tem sido pouco estudado pela literatura gastroenterológica e cirúrgica 21 . Porém, é de fundamental importância, pois as características deste tipo de litíase a transformam numa entidade clínica que necessita ser reconhecida precocemente, a fim de evitar intervenções cirúrgicas desnecessárias 9 14 .…”

Section: Relato Do Casounclassified

Colelitíase associada ao uso de ceftriaxona

Costa

Barbosa

2005

Rev. Soc. Bras. Med. Trop.

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RESUMOCriança de sete anos recebeu ceftriaxona para o tratamento de meningite, evoluindo com dor em hipocôndrio direito associada a cálculo na vesícula biliar. Após três meses, a ultrassonografia abdominal foi normal. O conhecimento de que a ceftriaxona pode levar ao surgimento de colelitíase pode evitar intervenções cirúrgicas desnecessárias. Palavras-chaves: Ceftriaxona. Colelitíase. Litíase. ABSTRACTA seven-year-old boy treated with ceftriaxone for meningitis who presented a right upper quadrant abdominal pain associated with cholelithiasis. After three months he was symptom-free and abdominal ultrasonography was normal. Awareness of this phenomenon is highly important and can save many unnecessary cholecystectomies. Key-words: Ceftriaxone. Cholelithiasis. Lithiasis. A ceftriaxona possui uma baixa absorção pelo trato gastrointestinal e deve ser administrada por via parenteral, sendo amplamente distribuída. Atinge concentrações adequadas no líquor, motivo pelo qual é efetiva no tratamento de meningites bacterianas 15 .Diferente da maioria das outras cefalosporinas, a ceftriaxona possui uma alta afinidade pelas proteínas, porém, o deslocamento da bilirrubina dos sítios de ligação protéicos é controverso 15 . A longa meia-vida da ceftriaxona, aproximadamente 6 a 9 horas nos adultos e 5 a 18 horas em crianças, possibilita a administração da droga em apenas 1 ou 2 doses diárias 2 15 21 .A principal forma de eliminação da ceftriaxona é renal, e em 40% pela via biliar, alcançando concentrações na bile de 20-150 vezes maiores que no sangue 12 .A ceftriaxona pode induzir à formação de lama biliar ou colelitíase em adultos e crianças, que usualmente é assintomática e tem involução completa após o término da medicação, sendo por isso, chamada de pseudocolelitíase 8 . Foi primeiramente descrita por Schaad em 1986 11 . Desde então, vários relatos se seguiram relacionando o uso de ceftriaxona com a calculose biliar e a lama biliar 3 11 12 13 16 19 21 sem relação com achados bioquímicos anormais, exceto pelos níveis séricos elevados de gama-glutamiltransferase 8 13 e de fosfatase alcalina 8 .Como o tema é pouco diagnosticado em nosso meio, apresentamos o relato de um caso. RELATO DO CASOMenino de 7 anos de idade, com história de febre baixa, vômitos esporádicos e cefaléia, recebeu o diagnóstico de meningite aguda e foi iniciado o tratamento com 3,5g/dia (135mg/Kg/dia) de ceftriaxona, divididos em duas doses diárias, administradas em bolus, durante 8 dias. No segundo dia de antibioticoterapia, apresentou dor intensa, tipo cólica, no hipocôndrio direito, sendo realizada ultrassonografia abdominal que revelou colelitíase (Figura 1).O tratamento foi mantido e, do quinto ao sétimo dia de uso do antibiótico, a criança apresentou febre e vômitos biliosos, além do quadro doloroso. Foi encaminhada ao cirurgião pediátrico que indicou a colecistectomia após a melhora clínica. Recebeu alta hospitalar após a resolução da meningite e foi encaminhado ao ambulatório de

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“…To control for any impact of serum components on bacterial growth and antibiotic activity, oritavancin activity in serum was compared to its activity in serum ultrafiltrate, which is devoid of albumin, the protein responsible for the majority of oritavancin serum binding (23). The method was benchmarked using daptomycin and ceftriaxone (8,18,22 Pooled serum from humans, mice, and rats was from Equitech-Bio (Kerrville, TX); pooled serum from beagle dogs was from Bioreclamation (Liverpool, NY). Serum ultrafiltrate was prepared using Centricon Plus-50 ultrafilters (Millipore, Billerica, MA), whose molecular mass cutoff (50 kDa) excludes albumin.…”

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confidence: 99%

“…To control for any impact of serum components on bacterial growth and antibiotic activity, oritavancin activity in serum was compared to its activity in serum ultrafiltrate, which is devoid of albumin, the protein responsible for the majority of oritavancin serum binding (23). The method was benchmarked using daptomycin and ceftriaxone (8,18,22). (Part of this work was previously presented at the 19th European Congress of Clinical Microbiology and Infectious Diseases as a poster [12].…”

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Assessment of Oritavancin Serum Protein Binding across Species

Arhin¹,

Belley²,

McKay³

et al. 2010

Antimicrob Agents Chemother

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Biophysical methods to study the binding of oritavancin, a lipoglycopeptide, to serum protein are confounded by nonspecific drug adsorption to labware surfaces. We assessed oritavancin binding to serum from mouse, rat, dog, and human by a microbiological growth-based method under conditions that allow near-quantitative drug recovery. Protein binding was similar across species, ranging from 81.9% in human serum to 87.1% in dog serum. These estimates support the translation of oritavancin exposure from nonclinical studies to humans.Estimates of serum protein binding are essential to translate drug exposure from nonclinical species to humans during assessments of toxicology, pharmacokinetics, and pharmacodynamics since the free fraction dictates drug activity (3,7,17,18). Recent evidence supports the concept of an "active fraction" that offers insight into the pharmacodynamic behavior of highly protein-bound drugs, such as daptomycin (20).Oritavancin is a late-stage investigational lipoglycopeptide under study for treatment of serious Gram-positive infections (6). Nonspecific binding of oritavancin to labware surfaces (1, 2) and to dialysis membranes has called into question the accuracy of previous oritavancin human serum binding estimates (85.7% to 89.9% [16]). We therefore used conditions that minimize nonspecific oritavancin binding (4, 5) to estimate its binding to serum by a single in vitro methodology for three nonclinical species (mouse, rat, and dog) and humans. Protein binding estimates were derived from serum-induced increases in oritavancin MICs (9, 10, 21). To control for any impact of serum components on bacterial growth and antibiotic activity, oritavancin activity in serum was compared to its activity in serum ultrafiltrate, which is devoid of albumin, the protein responsible for the majority of oritavancin serum binding (23). The method was benchmarked using daptomycin and ceftriaxone (8,18,22 Pooled serum from humans, mice, and rats was from Equitech-Bio (Kerrville, TX); pooled serum from beagle dogs was from Bioreclamation (Liverpool, NY). Serum ultrafiltrate was prepared using Centricon Plus-50 ultrafilters (Millipore, Billerica, MA), whose molecular mass cutoff (50 kDa) excludes albumin. MICs against Staphylococcus aureus ATCC 29213 were determined by broth microdilution (4) using arithmetic drug dilutions in 95% serum or 95% serum ultrafiltrate, each supplemented with 5% cation-adjusted Mueller-Hinton broth (CAMHB). Serum protein binding for each drug was calculated using the following formula: % bound ϭ (1 Ϫ [mean MIC in serum ultrafiltrate/mean MIC in serum]) ϫ 100.The MICs for each condition, serum source, and test agent were precise (Table 1), with a mean coefficient of variation of 17%. MICs as determined under CLSI M7-A8 conditions (Table 1) (4) were within the quality control ranges (5).Increases in the oritavancin MICs in serum compared to its MICs in serum ultrafiltrate, by species, were similar across species (5.5-to 7.8-fold) ( Table 2). Such shifts yielded similar mean values of or...

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Clinical Pharmacokinetics of Ceftriaxone

Cited by 63 publications

References 111 publications

Pharmacokinetics and protein binding of ceftriaxone during pregnancy

Pharmacokinetics and protein binding of ceftriaxone during pregnancy

Colelitíase associada ao uso de ceftriaxona

Assessment of Oritavancin Serum Protein Binding across Species

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