Disposition of Cefotaxime and its Desacetyl Metabolite in Morbidly Obese Male and Female Subjects

Yost, Richard L.; Derendorf, Hartmut

doi:10.1097/00007691-198606000-00011

Cited by 35 publications

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“…Because the MICs of cefotiam for most strains of clinically isolated E. coli, S. aulreuls, K. pnelimoniae, H. influenzae, and P. mirabilis are within a range of 0.2 to 0.78 pLg/ml (10), the pharmacokinetics of cefotiam described in this study suggest that an intraveneous dose of 1 g x (BSA/1.7 m2) and 2 g x (BSA/1.7 m2) infused over 30 min in the obese patient group would produce respective concentrations in plasma of greater than 0.78 p.g/ml (with respective peaks of 52.0 ± 10.7 and 103.9 ± 21.4 p.g/ml) for 3.72 ± 0.63 and 4.65 + 0.58 h after the infusion began and therefore would readily inhibit these bacterial pathogens for at least approximately 3.7 and 4.7 h, respectively. These values predicted from the mean disposition data in the sumo wrestler patient group are comparable to the respective values calculated after a 1-g dose (3.54 + 0.54 h) and actually observed after a 2-g dose of cefotiam (4. (21) describing cefotaxime kinetics in morbidly obese subjects. They found that kinetic parameters of cefotaxime in morbidly obese subjects can be compensated for if the parameters are corrected for BSA and recommended that a dosage adjustment of cefotaxime should be made on the basis of BSA (21).…”

Section: Methodsmentioning

confidence: 99%

“…These values predicted from the mean disposition data in the sumo wrestler patient group are comparable to the respective values calculated after a 1-g dose (3.54 + 0.54 h) and actually observed after a 2-g dose of cefotiam (4. (21) describing cefotaxime kinetics in morbidly obese subjects. They found that kinetic parameters of cefotaxime in morbidly obese subjects can be compensated for if the parameters are corrected for BSA and recommended that a dosage adjustment of cefotaxime should be made on the basis of BSA (21). The correlation of our findings with those of Yost and Derendorf may come from the similar physicochemical and pharmacokinetic properties of cefotiam and cefotaxime, since both cephalosporins have a common chemical structure (6).…”

Section: Methodsmentioning

confidence: 99%

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Cefotiam disposition in markedly obese athlete patients, Japanese sumo wrestlers

Chiba

Tsuchiya

Katô

et al. 1989

Antimicrob Agents Chemother

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Markedly obese athletes like Japanese sumo wrestlers may frequently suffer various traumas which result in the prophylaxis or treatment of posttraumatic infection with antibiotics. However, appropriate dosage regimens in this group of patients have not been fully known for many antibiotics. Therefore, we studied the kinetic disposition of cefotiam, a parenteral, broad-spectrum cephalosporin with activity against gram-positive and -negative bacteria, after an intravenous dose (2 g) infused over 30 min into 15 sumo wrestler patients with an excess body weight (130 to 220% of ideal body weight) and 10 control patients with a normal weight (90 to 102% of ideal body weight). Mean (± standard deviation) clearance and steady-state volume of distribution were significantly greater in the sumo wrestler than in the control group (38.3 ± 9.4 versus 23.5 ± 6.0 liters/h, P < 0.001, and 30.2 ± 8.0 versus 17.9 ± 6.1 liters, P < 0.001). Mean elimination half-life was slightly but significantly longer in the sumo wrestler than in the control group (0.91 ± 0.14 versus 0.74 ± 0.20 h, P < 0.05). However, mean residence time did not differ between the two groups (0.79 ± 0.10 versus 0.75 ± 0.14 h). The statistical differences in clearance and volume of distribution between the two groups disappeared when these kinetic parameters were corrected for body surface area, but not for total body weight or ideal body weight. The results suggest that the dosage calculation of cefotiam, a hydrophilic antibiotic, should be made on the basis of body surface area in morbidly obese athlete or sumo wrestler patients. However, whether this recommendation should extend to other nonathlete obese subjects remains to be determined.Sumo, a unique form of wrestling with a 2,000-year-old history, is the national sport of Japan (5, 18). There are more than 700 professional sumo wrestlers in the country. The most prominent physical characteristic of sumo wrestlers is obesity (5, 18). Since physical essentials for success in sumo wrestling are heavy weight and low center of gravity, wrestlers desire to gain weight and ingest many calories so that they have a tendency to be markedly obese. The heaviest professional sumo wrestler in the major league weighs 241 kg with a height of 187 cm.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Cefotiam disposition in markedly obese athlete patients, Japanese sumo wrestlers

Chiba

Tsuchiya

Katô

et al. 1989

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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“…The effect of altered body composition on drug disposition and therapeutic outcome with increasing obesity is particularly pertinent in antimicrobial therapy. Suboptimal drug exposure can lead to clinical failure and increase the risk of drug resistance.Several studies that specifically examined drug disposition of ␤-lactam antibiotics in obesity found an increase in the volume of distribution and/or drug clearance in obese subjects (3,12,24). This suggests that such patients may require higher doses or more frequent administration in order to achieve adequate drug exposure.…”

mentioning

confidence: 99%

“…Several studies that specifically examined drug disposition of ␤-lactam antibiotics in obesity found an increase in the volume of distribution and/or drug clearance in obese subjects (3,12,24). This suggests that such patients may require higher doses or more frequent administration in order to achieve adequate drug exposure.…”

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confidence: 99%

Comparative Pharmacokinetics and Pharmacodynamic Target Attainment of Ertapenem in Normal-Weight, Obese, and Extremely Obese Adults

Chen

Nafziger

Drusano

et al. 2006

Antimicrob Agents Chemother

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Little is known of the effects of obesity on ertapenem drug disposition and pharmacodynamics. Thirty healthy volunteers in three body mass index (BMI) groups (10 per group), normal weight (BMI, 18.5 to 24.9 kg/m 2 ), class I-II obesity (BMI, 30 to 39.9 kg/m 2 ), and class III obesity (BMI, >40 kg/m 2 ), were administered a 1-g dose of ertapenem. Serum concentrations were obtained over 24 h. Population pharmacokinetic data were obtained using a nonparametric adaptive grid followed by Monte Carlo simulation to determine the probability of obtaining the free drug exposure targets of the time that the free drug concentration remains above the MIC ( f T >MIC ) of 20% and 40% for bacteriostatic and maximal bactericidal activity, respectively. Compared to the subjects in the obese groups, area under the concentration-time curve from 0 h to infinity was significantly higher in the normal-weight subjects, whereas the total central compartment volume was higher in the class III obese subjects (P < 0.05). Achieving a bacteriostatic target of f T >MIC of 20% with a 90% probability was attained at MICs of <0.5 g/ml for normal-weight subjects. Class I-II and class III obese subjects were able to achieve this target only at a MIC of <0.25 g/ml. For maximal bactericidal activity ( f T >MIC , 40%), no group attained the target at the 90% probability level at any tested MIC. The results suggest that the standard 1-g ertapenem dose may not provide adequate drug exposure for any body mass index classification for MICs in excess of 0.25 to 0.5 g/ml.The prevalence of obesity is on the rise, and obesity has become an epidemic in many countries. In the United States alone, more than 44 million adults are obese (body mass index [BMI], Ն30 kg/m 2 ) (1), and some regional and ethnic groups of the population exhibit high rates of obesity. Recent data from the 1999 to 2002 National Health and Nutrition Examination Survey indicate that 65% of U.S. adults are either overweight or obese (2). Nevertheless, only a limited number of studies have been conducted that evaluate obesity-associated physiological changes and their pharmacokinetic (PK) ramifications. The effect of altered body composition on drug disposition and therapeutic outcome with increasing obesity is particularly pertinent in antimicrobial therapy. Suboptimal drug exposure can lead to clinical failure and increase the risk of drug resistance.Several studies that specifically examined drug disposition of ␤-lactam antibiotics in obesity found an increase in the volume of distribution and/or drug clearance in obese subjects (3,12,24). This suggests that such patients may require higher doses or more frequent administration in order to achieve adequate drug exposure.Ertapenem (Invanz) is a carbapenem antibiotic recommended for therapy (one gram once a day) of patients with appropriate renal function (creatinine clearance Ͼ30 ml/min/1.73 m 2 ) (19). Similar to other carbapenems, ertapenem demonstrates broadspectrum activity against gram-positive, gram-negative, and anaerobic pathogens...

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“…This phenomenon is magnified for lipophilic medications, which tend to more readily distribute than hydrophilic drugs. Previous work has identified larger V d in obese patients for most classes of antimicrobial agents, including penicillins, cephalosporins, carbapenems, aminoglycosides, vancomycin, and others [16][17][18][19][20][21][22][23][24][25]. The extent to which a medication is protein-bound also affects V d , and obesity has been shown to alter lipoproteins and alpha1-acid glycoprotein [2].…”

Section: Discussionmentioning

confidence: 99%

Obesity Is Not Associated with Antimicrobial Treatment Failure for Intra-Abdominal Infection

Dietch

Duane

Cook

et al. 2016

Surgical Infections

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Background: Obesity and commonly associated comorbidities are known risk factors for the development of infections. However, the intensity and duration of antimicrobial treatment are rarely conditioned on body mass index (BMI). In particular, the influence of obesity on failure of antimicrobial treatment for intra-abdominal infection (IAI) remains unknown. We hypothesized that obesity is associated with recurrent infectious complications in patients treated for IAI. Methods: Five hundred eighteen patients randomized to treatment in the Surgical Infection Society Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial were evaluated. Patients were stratified by obese (BMI ‡30) versus non-obese (BMI ‡30) status. Descriptive comparisons were performed using Chi-square test, Fisher exact test, or Wilcoxon rank-sum tests as appropriate. Multivariable logistic regression using a priori selected variables was performed to assess the independent association between obesity and treatment failure in patients with IAI. Results: Overall, 198 (38.3%) of patients were obese (BMI ‡30) versus 319 (61.7%) who were non-obese. Mean antibiotic d and total hospital d were similar between both groups. Unadjusted outcomes of surgical site infection (9.1% vs. 6.9%, p = 0.36), recurrent intra-abdominal infection (16.2% vs. 13.8, p = 0.46), death (1.0% vs. 0.9%, p = 1.0), and a composite of all complications (25.3% vs. 19.8%, p = 0.14) were also similar between both groups. After controlling for appropriate demographics, comorbidities, severity of illness, treatment group, and duration of antimicrobial therapy, obesity was not independently associated with treatment failure (c-statistic: 0.64). Conclusions: Obesity is not associated with antimicrobial treatment failure among patients with IAI. These results suggest that obesity may not independently influence the need for longer duration of antimicrobial therapy in treatment of IAI versus non-obese patients.

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Disposition of Cefotaxime and its Desacetyl Metabolite in Morbidly Obese Male and Female Subjects

Cited by 35 publications

References 0 publications

Cefotiam disposition in markedly obese athlete patients, Japanese sumo wrestlers

Cefotiam disposition in markedly obese athlete patients, Japanese sumo wrestlers

Comparative Pharmacokinetics and Pharmacodynamic Target Attainment of Ertapenem in Normal-Weight, Obese, and Extremely Obese Adults

Obesity Is Not Associated with Antimicrobial Treatment Failure for Intra-Abdominal Infection

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