The pharmacokinetics and toxicity of morning vs. evening tobramycin dosing for pulmonary exacerbations of cystic fibrosis: A randomised comparison
Circadian variation in renal toxicity of aminoglycosides has been demonstrated in animal and human studies. People with CF are frequently prescribed aminoglycosides. Altered pharmacokinetics of aminoglycosides are predictive of toxicity. To investigate whether the time of day of aminoglycoside admin...
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| Vydané v: | Journal of cystic fibrosis Ročník 15; číslo 4; s. 510 - 517 |
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| Hlavní autori: | , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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Netherlands
Elsevier B.V
01.07.2016
Elsevier |
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| ISSN: | 1569-1993, 1873-5010 |
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| Abstract | Circadian variation in renal toxicity of aminoglycosides has been demonstrated in animal and human studies. People with CF are frequently prescribed aminoglycosides. Altered pharmacokinetics of aminoglycosides are predictive of toxicity.
To investigate whether the time of day of aminoglycoside administration modulates renal excretion of tobramycin and toxicity in children with CF. To determine whether circadian rhythms are disrupted in children with CF during hospital admission.
Children (age 5–18years) with CF scheduled for tobramycin therapy were randomly allocated to receive tobramycin at 0800 or 2000h. Serum tobramycin levels were drawn at 1h and between 3.5 and 5h post-infusion between days 5 and 9 of therapy. Melatonin levels were measured serially at intervals from 1800h in the evening until 1200h on the next day. Circadian rhythm was categorised as normal when dim light melatonin onset was demonstrated between 1800 and 2200h and/or peak melatonin levels were observed during the night. Weight and spirometry were measured at the start and end of the therapy. Urinary biomarkers of kidney toxicity (KIM1, NAG, NGAL, IL-18 and CysC) were assayed at the start and end of the course of tobramycin.
Eighteen children were recruited to the study. There were no differences in renal clearance between the morning and evening groups. The increase in urinary KIM-1 was greater in the evening dosage group compared to the morning group (mean difference, 0.73ng/mg; 95% CI, 0.14 to 1.32; p=0.018). There were no differences in the other urinary biomarkers. There was normal circadian rhythm in 7/11 participants (64%).
Renal elimination of tobramycin was not affected by the time of day of administration. Urinary KIM-1 raises the possibility of greater nephrotoxicity with evening administration. Four children showed disturbed circadian rhythm and high melatonin levels (ClinicalTrials.gov NCT01207245).
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| AbstractList | Circadian variation in renal toxicity of aminoglycosides has been demonstrated in animal and human studies. People with CF are frequently prescribed aminoglycosides. Altered pharmacokinetics of aminoglycosides are predictive of toxicity.
To investigate whether the time of day of aminoglycoside administration modulates renal excretion of tobramycin and toxicity in children with CF. To determine whether circadian rhythms are disrupted in children with CF during hospital admission.
Children (age 5-18years) with CF scheduled for tobramycin therapy were randomly allocated to receive tobramycin at 0800 or 2000h. Serum tobramycin levels were drawn at 1h and between 3.5 and 5h post-infusion between days 5 and 9 of therapy. Melatonin levels were measured serially at intervals from 1800h in the evening until 1200h on the next day. Circadian rhythm was categorised as normal when dim light melatonin onset was demonstrated between 1800 and 2200h and/or peak melatonin levels were observed during the night. Weight and spirometry were measured at the start and end of the therapy. Urinary biomarkers of kidney toxicity (KIM1, NAG, NGAL, IL-18 and CysC) were assayed at the start and end of the course of tobramycin.
Eighteen children were recruited to the study. There were no differences in renal clearance between the morning and evening groups. The increase in urinary KIM-1 was greater in the evening dosage group compared to the morning group (mean difference, 0.73ng/mg; 95% CI, 0.14 to 1.32; p=0.018). There were no differences in the other urinary biomarkers. There was normal circadian rhythm in 7/11 participants (64%).
Renal elimination of tobramycin was not affected by the time of day of administration. Urinary KIM-1 raises the possibility of greater nephrotoxicity with evening administration. Four children showed disturbed circadian rhythm and high melatonin levels (ClinicalTrials.gov NCT01207245). Circadian variation in renal toxicity of aminoglycosides has been demonstrated in animal and human studies. People with CF are frequently prescribed aminoglycosides. Altered pharmacokinetics of aminoglycosides are predictive of toxicity. To investigate whether the time of day of aminoglycoside administration modulates renal excretion of tobramycin and toxicity in children with CF. To determine whether circadian rhythms are disrupted in children with CF during hospital admission. Children (age 5–18years) with CF scheduled for tobramycin therapy were randomly allocated to receive tobramycin at 0800 or 2000h. Serum tobramycin levels were drawn at 1h and between 3.5 and 5h post-infusion between days 5 and 9 of therapy. Melatonin levels were measured serially at intervals from 1800h in the evening until 1200h on the next day. Circadian rhythm was categorised as normal when dim light melatonin onset was demonstrated between 1800 and 2200h and/or peak melatonin levels were observed during the night. Weight and spirometry were measured at the start and end of the therapy. Urinary biomarkers of kidney toxicity (KIM1, NAG, NGAL, IL-18 and CysC) were assayed at the start and end of the course of tobramycin. Eighteen children were recruited to the study. There were no differences in renal clearance between the morning and evening groups. The increase in urinary KIM-1 was greater in the evening dosage group compared to the morning group (mean difference, 0.73ng/mg; 95% CI, 0.14 to 1.32; p=0.018). There were no differences in the other urinary biomarkers. There was normal circadian rhythm in 7/11 participants (64%). Renal elimination of tobramycin was not affected by the time of day of administration. Urinary KIM-1 raises the possibility of greater nephrotoxicity with evening administration. Four children showed disturbed circadian rhythm and high melatonin levels (ClinicalTrials.gov NCT01207245). [Display omitted] Abstract Background Circadian variation in renal toxicity of aminoglycosides has been demonstrated in animal and human studies. People with CF are frequently prescribed aminoglycosides. Altered pharmacokinetics of aminoglycosides are predictive of toxicity. Aim To investigate whether the time of day of aminoglycoside administration modulates renal excretion of tobramycin and toxicity in children with CF. To determine whether circadian rhythms are disrupted in children with CF during hospital admission. Methods Children (age 5–18 years) with CF scheduled for tobramycin therapy were randomly allocated to receive tobramycin at 0800 or 2000 h. Serum tobramycin levels were drawn at 1 h and between 3.5 and 5 h post-infusion between days 5 and 9 of therapy. Melatonin levels were measured serially at intervals from 1800 h in the evening until 1200 h on the next day. Circadian rhythm was categorised as normal when dim light melatonin onset was demonstrated between 1800 and 2200 h and/or peak melatonin levels were observed during the night. Weight and spirometry were measured at the start and end of the therapy. Urinary biomarkers of kidney toxicity (KIM1, NAG, NGAL, IL-18 and CysC) were assayed at the start and end of the course of tobramycin. Results Eighteen children were recruited to the study. There were no differences in renal clearance between the morning and evening groups. The increase in urinary KIM-1 was greater in the evening dosage group compared to the morning group (mean difference, 0.73 ng/mg; 95% CI, 0.14 to 1.32; p = 0.018). There were no differences in the other urinary biomarkers. There was normal circadian rhythm in 7/11 participants (64%). Conclusions Renal elimination of tobramycin was not affected by the time of day of administration. Urinary KIM-1 raises the possibility of greater nephrotoxicity with evening administration. Four children showed disturbed circadian rhythm and high melatonin levels (ClinicalTrials.gov NCT01207245). BACKGROUNDCircadian variation in renal toxicity of aminoglycosides has been demonstrated in animal and human studies. People with CF are frequently prescribed aminoglycosides. Altered pharmacokinetics of aminoglycosides are predictive of toxicity.AIMTo investigate whether the time of day of aminoglycoside administration modulates renal excretion of tobramycin and toxicity in children with CF. To determine whether circadian rhythms are disrupted in children with CF during hospital admission.METHODSChildren (age 5-18years) with CF scheduled for tobramycin therapy were randomly allocated to receive tobramycin at 0800 or 2000h. Serum tobramycin levels were drawn at 1h and between 3.5 and 5h post-infusion between days 5 and 9 of therapy. Melatonin levels were measured serially at intervals from 1800h in the evening until 1200h on the next day. Circadian rhythm was categorised as normal when dim light melatonin onset was demonstrated between 1800 and 2200h and/or peak melatonin levels were observed during the night. Weight and spirometry were measured at the start and end of the therapy. Urinary biomarkers of kidney toxicity (KIM1, NAG, NGAL, IL-18 and CysC) were assayed at the start and end of the course of tobramycin.RESULTSEighteen children were recruited to the study. There were no differences in renal clearance between the morning and evening groups. The increase in urinary KIM-1 was greater in the evening dosage group compared to the morning group (mean difference, 0.73ng/mg; 95% CI, 0.14 to 1.32; p=0.018). There were no differences in the other urinary biomarkers. There was normal circadian rhythm in 7/11 participants (64%).CONCLUSIONSRenal elimination of tobramycin was not affected by the time of day of administration. Urinary KIM-1 raises the possibility of greater nephrotoxicity with evening administration. Four children showed disturbed circadian rhythm and high melatonin levels (ClinicalTrials.gov NCT01207245). |
| Author | Prayle, A.P. Jain, K. Knox, A.J. Touw, D.J. Koch, B.C.P. Smyth, A.R. Watson, A. |
| AuthorAffiliation | a The University of Nottingham, Nottingham, United Kingdom c Erasmus Medical Centre, Rotterdam, Netherlands d Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom b The University of Groningen, Groningen, Netherlands |
| AuthorAffiliation_xml | – name: a The University of Nottingham, Nottingham, United Kingdom – name: c Erasmus Medical Centre, Rotterdam, Netherlands – name: b The University of Groningen, Groningen, Netherlands – name: d Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom |
| Author_xml | – sequence: 1 givenname: A.P. surname: Prayle fullname: Prayle, A.P. organization: The University of Nottingham, Nottingham, United Kingdom – sequence: 2 givenname: K. surname: Jain fullname: Jain, K. organization: The University of Nottingham, Nottingham, United Kingdom – sequence: 3 givenname: D.J. surname: Touw fullname: Touw, D.J. organization: The University of Groningen, Groningen, Netherlands – sequence: 4 givenname: B.C.P. surname: Koch fullname: Koch, B.C.P. organization: Erasmus Medical Centre, Rotterdam, Netherlands – sequence: 5 givenname: A.J. surname: Knox fullname: Knox, A.J. organization: The University of Nottingham, Nottingham, United Kingdom – sequence: 6 givenname: A. surname: Watson fullname: Watson, A. organization: Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom – sequence: 7 givenname: A.R. surname: Smyth fullname: Smyth, A.R. organization: The University of Nottingham, Nottingham, United Kingdom |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26282839$$D View this record in MEDLINE/PubMed |
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| Copyright | 2015 Copyright © 2015. Published by Elsevier B.V. 2015 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. 2015 |
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| Keywords | Cystic fibrosis Aminoglycosides Circadian rhythm Toxicity |
| Language | English |
| License | This is an open access article under the CC BY-NC-ND license. Copyright © 2015. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
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| Snippet | Circadian variation in renal toxicity of aminoglycosides has been demonstrated in animal and human studies. People with CF are frequently prescribed... Abstract Background Circadian variation in renal toxicity of aminoglycosides has been demonstrated in animal and human studies. People with CF are frequently... BACKGROUNDCircadian variation in renal toxicity of aminoglycosides has been demonstrated in animal and human studies. People with CF are frequently prescribed... |
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| SubjectTerms | Adolescent Aminoglycosides Aminoglycosides - administration & dosage Aminoglycosides - adverse effects Aminoglycosides - pharmacokinetics Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - adverse effects Anti-Bacterial Agents - pharmacokinetics Child Circadian rhythm Circadian Rhythm - physiology Cystic fibrosis Cystic Fibrosis - drug therapy Drug Administration Schedule Drug Chronotherapy Drug Monitoring - methods Female Hepatitis A Virus Cellular Receptor 1 - analysis Humans Kidney - drug effects Kidney - metabolism Male Melatonin - analysis Original Pulmonary/Respiratory Renal Elimination - physiology Tobramycin - administration & dosage Tobramycin - adverse effects Tobramycin - pharmacokinetics Toxicity Treatment Outcome Urinalysis - methods |
| Title | The pharmacokinetics and toxicity of morning vs. evening tobramycin dosing for pulmonary exacerbations of cystic fibrosis: A randomised comparison |
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