Pharmacokinetic and Pharmacodynamic Aspects of Antibiotic Use in High-Risk Populations

Bergman, Scott; Speil, C.A.; Short, Michael; Koirala, Janak

doi:10.1016/j.idc.2007.07.004

Cited by 27 publications

(30 citation statements)

References 126 publications

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“…Because transporters are responsible for a significant phase of chemical handling, this observed change in transporter expression implies that obese mice should have differential patterns of chemical absorption and elimination. Multiple drugs show altered pharmacokinetics and toxicokinetics in obese patients and the underlying reasons for altered pharmacokinetics in obese patients have not been well defined, but alterations in drug transporter expression could contribute to these observations (Bergman et al, 2007;Edelman et al, 2009). Abernethy et al (1986 reported altered disposition of nitrazepam in obese human subjects.…”

Section: Downloaded Frommentioning

confidence: 99%

Alteration of Hepatic but Not Renal Transporter Expression in Diet-Induced Obese Mice

Slitt

2011

Drug Metab Dispos

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ABSTRACT:Drug pharmacokinetics can be altered in obese and diabetic subjects. In consideration of the prevalence of obesity and diabetes, characterization of transporter expression in mouse models of diabetes and obesity may be a useful tool to aid in prediction of altered drug pharmacokinetics or adverse drug reactions. It has been reported that ob/ob mice, which display a severe obesity and diabetes phenotype, exhibit multiple changes in drug transporter expression in liver and kidney. In the present study, the mRNA and protein expression of major drug transporters was determined in livers and kidneys of diet-induced obese (DIO) C57BL/6J male mice. The mice were fed a high-fat diet (HFD) (60% fat) from 6 weeks of age and display obesity, fatty liver, and mild hyperglycemia. The HFD diet increased expression of multidrug resistanceassociated proteins Abcc3 and 4 mRNA and protein in liver by 3.4-and 1.4-fold, respectively, compared with that detected in control mice fed a low-fat diet (LFD). In contrast, Abcc1 mRNA and protein decreased by 50% in livers of DIO mice compared with those in livers to lean mice. The HFD did not alter transporter expression in kidney compared with the LFD. In summary, unlike ob/ob and db/db mice, DIO mice exhibited a selective induction of efflux transporter expression in liver (i.e., Abcc3 and 4). In addition, dietinduced obesity affects transporter expression in liver but not kidney in the C57BL/6J mouse model. These data indicate that hepatic transporter expression is only slightly altered in a model of mild diabetes and nonalcoholic fatty liver disease and obesity.

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Section: Downloaded Frommentioning

confidence: 99%

Alteration of Hepatic but Not Renal Transporter Expression in Diet-Induced Obese Mice

Slitt

2011

Drug Metab Dispos

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“…Many antibacterials necessitate adjustments to dose size, dose frequency, or both when patients with impaired renal or hepatic function are treated (10,11) because chronic kidney disease and serious liver disease cause complex changes to the metabolism and elimination of many antibacterials (10,11). These disorders are also associated with increased risk of serious infections, including those due to drug-resistant Gram-positive pathogens (10,12,13), and clinically significant adverse effects caused by antibacterial treatment itself (10,14,15).…”

mentioning

confidence: 99%

“…These disorders are also associated with increased risk of serious infections, including those due to drug-resistant Gram-positive pathogens (10,12,13), and clinically significant adverse effects caused by antibacterial treatment itself (10,14,15). Because of aging populations, the prevalences of chronic kidney disease (16) and chronic liver disease (17) are increasing.…”

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confidence: 99%

Pharmacokinetics of Tedizolid in Subjects with Renal or Hepatic Impairment

Flanagan

Minassian

Morris

et al. 2014

Antimicrob Agents Chemother

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Two open-label, single-dose, parallel-group studies were conducted to characterize the pharmacokinetics of the novel antibacterial tedizolid and the safety of tedizolid phosphate, its prodrug, in renally or hepatically impaired subjects. Tedizolid pharmacokinetics in subjects with severe renal impairment without dialysis support was compared with that of matched control subjects with normal renal function. Effects of hemodialysis on tedizolid pharmacokinetics were determined in a separate cohort of subjects undergoing long-term hemodialysis. Effects of hepatic impairment on tedizolid pharmacokinetics were determined in subjects with moderate or severe hepatic impairment and compared with those of matched control subjects with normal hepatic function. Each participant received a single oral (hepatic impairment) or intravenous (renal impairment) dose of tedizolid phosphate at 200 mg; hemodialysis subjects received two doses (separated by 7 days), before and after dialysis, in a crossover fashion. The pharmacokinetics of tedizolid was similar in subjects with severe renal impairment and controls (ϳ8% lower area under the concentration-time curve [AUC], with a nearly identical peak concentration) and in subjects undergoing hemodialysis before and after tedizolid phosphate administration (ϳ9% lower AUC, with a 15% higher peak concentration); <10% of the dose was removed during 4 h of hemodialysis. Tedizolid pharmacokinetics was only minimally altered in subjects with moderate or severe hepatic impairment; the AUC was increased approximately 22% and 34%, respectively, compared with that of subjects in the control group. Tedizolid phosphate was generally well tolerated in all participants. These results suggest that tedizolid phosphate dose adjustments are not necessary in patients with any degree of renal or hepatic impairment. (This study has been registered at ClinicalTrials.gov under registration numbers NCT01452828 [renal study] and NCT01431833 [hepatic study].)

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“…Wenn die Leberfunktion beeinträchtigt ist, muss die Dosis hepatisch metabolisierter und eliminierter Substanzen reduziert werden [6-8, 14, 28] [3]. Dies wird durch das Verhältnis der Fläche unter der Zeit-KonzentrationsKurve zur MHK (AUC/MHK) ausgedrückt [9,26]. Im Gegensatz dazu ist bei konzentrationsabhängig wirkenden Antibiotika (z.…”

Section: Introductionunclassified

“…Im Gegensatz dazu ist bei konzentrationsabhängig wirkenden Antibiotika (z. B. Aminoglykosiden) das Verhältnis der Spitzenkonzentration (Cmax) zur MHK maßgeblich [8,9,26]. Bei Substanzen mit schmaler therapeutischer Breite ist ein therapeutisches Drugmonitoring dringend anzuraten.…”

Section: Introductionunclassified

Personalisierte Pharmakotherapie beim Intensivpatienten

Bellmann

2017

Med Klin Intensivmed Notfmed

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Pharmacokinetic and Pharmacodynamic Aspects of Antibiotic Use in High-Risk Populations

Cited by 27 publications

References 126 publications

Alteration of Hepatic but Not Renal Transporter Expression in Diet-Induced Obese Mice

Alteration of Hepatic but Not Renal Transporter Expression in Diet-Induced Obese Mice

Pharmacokinetics of Tedizolid in Subjects with Renal or Hepatic Impairment

Personalisierte Pharmakotherapie beim Intensivpatienten

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