Population pharmacokinetic study of ceftriaxone in elderly patients, using cystatin C-based estimates of renal function to account for frailty
Ceftriaxone is widely used for respiratory and urinary infections in elderly and frail patients, but there are few pharmacokinetic studies. A prospective population pharmacokinetic study of ceftriaxone in adults over 65 years old was undertaken. Dried blood spots collected at baseline (predose) and...
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| Format: | Journal Article |
| Language: | English |
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AMER SOC MICROBIOLOGY
2020
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| Online Access: | http://purl.org/au-research/grants/nhmrc/1047105 http://hdl.handle.net/20.500.11937/88948 |
| _version_ | 1848765121774485504 |
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| author | Tan, S.J. Cockcroft, M. Page-Sharp, Madhu Arendts, G. Davis, T.M.E. Moore, Brioni Batty, Kevin Salman, S. Manning, L. |
| author_facet | Tan, S.J. Cockcroft, M. Page-Sharp, Madhu Arendts, G. Davis, T.M.E. Moore, Brioni Batty, Kevin Salman, S. Manning, L. |
| author_sort | Tan, S.J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Ceftriaxone is widely used for respiratory and urinary infections in elderly and frail patients, but there are few pharmacokinetic studies. A prospective population pharmacokinetic study of ceftriaxone in adults over 65 years old was undertaken. Dried blood spots collected at baseline (predose) and 0.5, 1, 4, 8, and 24 h after administration of 1 g of ceftriaxone were assayed using a validated liquid chromatography-mass spectroscopy analytical method. Frailty was classified using the Edmonton frailty scale and grip strength via a hand dynamometer. Estimates of glomerular filtration rate were determined using creatinine-based and cystatin C-based equations. Of 26 patients recruited, 23 (88%) were vulnerable or very frail. Estimates of drug clearance improved significantly with a cystatin C-based estimate of renal function that accounted for frailty. Simulations indicate that the combined effects of ranges of size and renal function resulted in a 6-fold range in peak ceftriaxone concentrations and 9-fold range in total exposure (area under the concentration-time curve [AUC]). For elderly patients with moderate or severe renal impairment, 48-h dosing results in greater trough concentrations and total exposure than the trough concentrations and total exposure in patients with normal renal function receiving 24-h dosing. Cystatin C-based measures of renal function improved predictions of ceftriaxone clearance in elderly patients. |
| first_indexed | 2025-11-14T11:30:13Z |
| format | Journal Article |
| id | curtin-20.500.11937-88948 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:30:13Z |
| publishDate | 2020 |
| publisher | AMER SOC MICROBIOLOGY |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-889482022-08-05T07:18:08Z Population pharmacokinetic study of ceftriaxone in elderly patients, using cystatin C-based estimates of renal function to account for frailty Tan, S.J. Cockcroft, M. Page-Sharp, Madhu Arendts, G. Davis, T.M.E. Moore, Brioni Batty, Kevin Salman, S. Manning, L. Science & Technology Life Sciences & Biomedicine Microbiology Pharmacology & Pharmacy ceftriaxone frailty population pharmacokinetics GLOMERULAR-FILTRATION-RATE SERUM CREATININE COCKCROFT-GAULT CLEARANCE EQUATIONS IMPACT PREDICTION SIZE Ceftriaxone is widely used for respiratory and urinary infections in elderly and frail patients, but there are few pharmacokinetic studies. A prospective population pharmacokinetic study of ceftriaxone in adults over 65 years old was undertaken. Dried blood spots collected at baseline (predose) and 0.5, 1, 4, 8, and 24 h after administration of 1 g of ceftriaxone were assayed using a validated liquid chromatography-mass spectroscopy analytical method. Frailty was classified using the Edmonton frailty scale and grip strength via a hand dynamometer. Estimates of glomerular filtration rate were determined using creatinine-based and cystatin C-based equations. Of 26 patients recruited, 23 (88%) were vulnerable or very frail. Estimates of drug clearance improved significantly with a cystatin C-based estimate of renal function that accounted for frailty. Simulations indicate that the combined effects of ranges of size and renal function resulted in a 6-fold range in peak ceftriaxone concentrations and 9-fold range in total exposure (area under the concentration-time curve [AUC]). For elderly patients with moderate or severe renal impairment, 48-h dosing results in greater trough concentrations and total exposure than the trough concentrations and total exposure in patients with normal renal function receiving 24-h dosing. Cystatin C-based measures of renal function improved predictions of ceftriaxone clearance in elderly patients. 2020 Journal Article http://hdl.handle.net/20.500.11937/88948 10.1128/AAC.00874-20 English http://purl.org/au-research/grants/nhmrc/1047105 http://purl.org/au-research/grants/nhmrc/1036951 http://purl.org/au-research/grants/nhmrc/1124130 AMER SOC MICROBIOLOGY fulltext |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Microbiology Pharmacology & Pharmacy ceftriaxone frailty population pharmacokinetics GLOMERULAR-FILTRATION-RATE SERUM CREATININE COCKCROFT-GAULT CLEARANCE EQUATIONS IMPACT PREDICTION SIZE Tan, S.J. Cockcroft, M. Page-Sharp, Madhu Arendts, G. Davis, T.M.E. Moore, Brioni Batty, Kevin Salman, S. Manning, L. Population pharmacokinetic study of ceftriaxone in elderly patients, using cystatin C-based estimates of renal function to account for frailty |
| title | Population pharmacokinetic study of ceftriaxone in elderly patients, using cystatin C-based estimates of renal function to account for frailty |
| title_full | Population pharmacokinetic study of ceftriaxone in elderly patients, using cystatin C-based estimates of renal function to account for frailty |
| title_fullStr | Population pharmacokinetic study of ceftriaxone in elderly patients, using cystatin C-based estimates of renal function to account for frailty |
| title_full_unstemmed | Population pharmacokinetic study of ceftriaxone in elderly patients, using cystatin C-based estimates of renal function to account for frailty |
| title_short | Population pharmacokinetic study of ceftriaxone in elderly patients, using cystatin C-based estimates of renal function to account for frailty |
| title_sort | population pharmacokinetic study of ceftriaxone in elderly patients, using cystatin c-based estimates of renal function to account for frailty |
| topic | Science & Technology Life Sciences & Biomedicine Microbiology Pharmacology & Pharmacy ceftriaxone frailty population pharmacokinetics GLOMERULAR-FILTRATION-RATE SERUM CREATININE COCKCROFT-GAULT CLEARANCE EQUATIONS IMPACT PREDICTION SIZE |
| url | http://purl.org/au-research/grants/nhmrc/1047105 http://purl.org/au-research/grants/nhmrc/1047105 http://purl.org/au-research/grants/nhmrc/1047105 http://hdl.handle.net/20.500.11937/88948 |