Pharmacokinetics of cefotaxime

Fu, Kwung P.; Aswapokee, P; Ho, Irwin; Matthijssen, Charles; Neu, Harold C.

doi:10.1128/aac.16.5.592

Cited by 75 publications

(36 citation statements)

References 10 publications

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“…The major route of elimination for moxalactam is via the kidneys. We found a mean of 61% in the urine, which is similar to the 55 to 76% reported by others (24,29,32,35 (7,9,10,12,22) and 76.1 min calculated from our own data, is much more rapid than that of cefoperazone (1,6,33,34) and moxalactam (19,29,35,36 Elimination of cefotaxime is rapid, with about 90% of the dose recovered in urine by HPLC, of which two-thirds is detected as unchanged cefotaxime and one-third as the major metabolite desacetyl cefotaxime. Bax et al (2) reported a total urine recovery of 87% with 35% as desacetylated metabolite, compared with a total recovery rate of 89.6% with 29.1% as metabolite in our study.…”

Section: Methodssupporting

confidence: 77%

See 1 more Smart Citation

Comparative pharmacokinetics of cefoperazone, cefotaxime, and moxalactam

Kemmerich¹,

Lode²,

Belmega³

et al. 1983

Antimicrob Agents Chemother

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The pharmacokinetics of cefoperazone, cefotaxime, and moxalactam were compared in a cross-over randomized study in 10 healthy volunteers. Each subject received 1.0 g of the three drugs by bolus intravenous injection over 3 min. Serum and urine concentrations were assayed by a microbiological method and in addition by high-pressure liquid chromatography (HPLC) for cefotaxime in five subjects. Maximal concentrations in serum 5 min after the injection were 163 ± 40.3 mg/liter for cefoperazone, 86.1 ± 19.0 mg/liter for cefotaxime, and 95.5 ± 21.1 mg/liter for moxalactam. After 12 h, 1.2 ± 1.4 mg of cefoperazone per liter and 1.8 ± 0.9 mg of moxalactam per liter could still be measured. Eight hours after the administration of cefotaxime, serum concentrations were below the detection limit of 0.3 mg/liter in most subjects. By HPLC analysis, the mean maximal concentration of desacetyl cefotaxime was 16.6 ± 10.5 mg/liter 5 min after application; the metabolite exceeded the serum concentration of the parent compound after 1 to 2 h. Relevant pharmacokinetic parameters were calculated, using two-and three-compartment models. The terminal half-life was 144.1 ± 37.3 min for cefoperazone, 76.1 ± 32.0 min for cefotaxime, and 272.4 ± 114.1 min for moxalactam. The apparent volume of distribution corresponded to the extracellular volume. Only 25.1 ± 8% of cefoperazone could be detected in urine compared with 53.3 ± 8.1% of cefotaxime and 61.0 ± 9.2% of moxalactam in 24 h. A total of 89.6 ± 11.4% of the cefotaxime dose could be recovered by HPLC in urine, 60.6 ± 7.7% as cefotaxime and 29.1 ± 7.0% as desacetyl cefotaxime.Cefoperazone, cefotaxime, and moxalactam are three newly developed cephalosporins with a high level of resistance to P-lactamase hydrolysis and a broad range of antibacterial action (13,18,28). The purpose of the present study was to compare the pharmacokinetics of these cephalosporins after a single intravenous (i.v.) bolus injection. MATERIALS AND METHODSSubjects. Ten healthy volunteers, five males and five females, 21 to 51 years of age (mean, 32 years of age), 44 to 82 kg (mean, 66.7 kg), participated as test subjects. Informed written consent was obtained from each subject.Administration of antibiotics. Cefoperazone sodium (Ch.-BI 130) was supplied by Pfizer GmbH, Karlsruhe, Federal Republic of Germany; moxalactam disodium (Ch.-BI-4473-9C) by E. Lilly Giessen, and cefotaxime (batch no. 100 N31) by Hoechst AG, Frankfurt, Federal Republic of Germany. The compounds were reconstituted in sterile water just before administration. Each subject received 1.0 g of cefoperazone, cefotaxime, and moxalactam by an i.v. injection over 3 min. The antibiotics were given by random allotment with a 1-to 2-week interval between the injections.Sampling. Blood samples were taken over 12 h: before injection; after 5, 10, 20, 30, and 45 min; and after 1, 1.5, 2, 3, 4, 6, 8, and 12 h. Blood specimens were centrifuged at 4°C after clotting at room temperature. Urine was collected 0 to 3, 3 to 6, 6 to 12, and 12 to 24 h after dosage.An...

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Section: Methodssupporting

confidence: 77%

“…Blood samples were taken over 12 h: before injection; after 5,10,20,30, and 45 min; and after 1, 1.5, 2, 3, 4, 6, 8, and 12 h. Blood specimens were centrifuged at 4°C after clotting at room temperature. Urine was collected 0 to 3, 3 to 6, 6 to Urinary excretion.…”

Section: Methodsmentioning

confidence: 99%

Comparative pharmacokinetics of cefoperazone, cefotaxime, and moxalactam

Kemmerich¹,

Lode²,

Belmega³

et al. 1983

Antimicrob Agents Chemother

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“…The human pharmacology of cefotaxime is similar to that of most currently available cephalosporins, but its half-life of approximately 1 h is twice as long as that of cephalothin (7,14,19). The serum levels after 1 g (Table 3) are in agreement with previously published findings, including the presence of residual antimicrobial activity up to 6 h after dosing (8,14,19 levels for up to 6 h after i.v.…”

Section: Discussionmentioning

confidence: 85%

Clinical evaluation of cefotaxime for therapy of lower respiratory tract infections

Schleupner¹,

Engle²

1982

Antimicrob Agents Chemother

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A clinical trial was designed to evaluate the efficacy and safety of cefotaxime, a new semisynthetic, broad-spectrum cephalosporin, in the therapy of communityand hospital-acquired pneumonias. Thirty-nine males (mean age, 65 years) were treated for 41 episodes of pneumonia. Only five patients did not have a serious underlying disease; 15 had two or more significant disorders. Sixty-six percent of these pneumonias were due to Streptococcus pneumoniae or Haemophilus influenzae. The minimal inhibitory concentrations for all bacterial isolates ranged from 0.008 to 4 ,ug/ml. Peak serum cefotaxime levels during therapy ranged from 12 to 124 ,ug/ml 1 h after a 1-g dose. Satisfactory bacteriological and clinical responses were observed in 85% of the cases. Four episodes of pulmonary superinfections due to cefotaxime-resistant gram-negative bacilli were noted, each in a patient being mechanically ventilated. Pseudomonas was involved in each of these superinfections, and three were fatal. No serious toxicity or adverse reaction to cefotaxime was seen. The results of this study suggest that cefotaxime is an effective and well-tolerated new cephalosporin antimicrobial agent for the therapy of pneumonia due to susceptible organisms.

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“…The pharmacokinetic parameters after single injection have been presented in several species such as rats (3), sheep (4), goats (5), calves (6), cats (7), dogs (8), and humans (9). An approximate serum half-life of 1.1-1.3 h after injection was confirmed in different studies (10)(11)(12)(13). The drug is primarily eliminated by the kidney, but also converted into the less active metabolite desacetyl-cefotaxime in the liver to a significant level (14)(15).…”

Section: Introductionmentioning

confidence: 86%

Nanosized Liposomes Containing Bile Salt: A Vesicular Nanocarrier for Enhancing Oral Bioavailability of BCS Class III Drug

et al. 2017

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-PURPOSE: Liposomes have been studied as a colloidal carrier in drug delivery systems, especially for oral administration. However, their low structural integrity in the gut is still a major shortcoming. Membrane disruptive effects of physiological bile salts in the small intestine result in premature drug release prior to intestinal absorption. Thus, we analyzed the stabilizing effect of sodium deoxycholate when incorporated into nano-sized liposomes. METHOD: Cefotaxime-loaded liposomes were prepared with different sodium deoxycholate concentrations (3.75-30 mM) by rotary film evaporation followed by nanosize reduction. The physical integrity of liposomes was evaluated by monitoring cefotaxime leakage, particle sizes in different simulated physiological media. The oral bioavailability and pharmacokinetics of cefotaxime was assessed in rats (n = 6 per group) after single dose of drug-encapsulated in liposomes containing bile salt, drug in conventional liposomes, and cefotaxime solution (oral and intravenous). RESULTS: Simulated gastric fluid with low pH showed less effect on the stability of liposomes in comparison to media containing physiological bile salts. Liposomes containing 15 mM sodium deoxycholate were most stable in size and retained the majority of encapsulated cefotaxime even in fed state of simulated intestinal fluid being the most destructive media. Pharmacokinetics data showed an increase in Cmax and AUC0-inf in the following order: cefotaxime solution < conventional liposomes < liposomes made with bile salts. The total oral bioavailability of cefotaxime in liposomes containing bile salt was found to be 5-times higher compared to cefotaxime solution and twice as much as in conventional liposomes. CONCLUSION: Incorporation of bile salts, initially used as membrane permeation enhancer, also acted as a stabilizer against physiological bile salts. The nanosized liposomes containing sodium deoxycholate were able to reduce the leakage of encapsulated cefotaxime in the gut due to the improved vesicle stability and to enhance the oral bioavailability of acid-labile drugs up to 5-fold.

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Pharmacokinetics of cefotaxime

Cited by 75 publications

References 10 publications

Comparative pharmacokinetics of cefoperazone, cefotaxime, and moxalactam

Comparative pharmacokinetics of cefoperazone, cefotaxime, and moxalactam

Clinical evaluation of cefotaxime for therapy of lower respiratory tract infections

Nanosized Liposomes Containing Bile Salt: A Vesicular Nanocarrier for Enhancing Oral Bioavailability of BCS Class III Drug

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