Pharmacokinetic studies of imipenem/cilastatin in elderly patients

Finch, Roger; Craddock, Charles; Kelly, J.G.; Deaney, N. B.

doi:10.1093/jac/18.supplement_e.103

Cited by 8 publications

(10 citation statements)

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“…It is therefore coadministered as a one-to-one combination with the DHP I inhibitor cilastatin, which results in the excretion of about 70% of unchanged imipenem into the urine (25) and a reduction in renal toxicity (18). In healthy volunteers and patients with normal renal function, both agents have almost identical pharmacokinetic properties (8,9,26). In patients with renal insufficiency (acute renal failure [ARF] and end-stage renal failure [ESRF]), however, the elimination of both drugs is differently affected, resulting in a much higher accumulation of cilastatin (11).…”

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confidence: 99%

Pharmacokinetics of imipenem-cilastatin in critically ill patients undergoing continuous venovenous hemofiltration

Tegeder

Bremer

Oelkers

et al. 1997

Antimicrob Agents Chemother

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The pharmacokinetics of imipenem-cilastatin were investigated in 12 critically ill patients with acute renal failure (ARF) managed by continuous veno-venous hemofiltration (CVVH) while receiving a fixed combination of 500 mg of imipenem-cilastatin intravenously three or four times daily. No adverse drug reactions were observed. Plasma and hemofiltrate samples were taken at specified times during one dosing interval, and the concentrations of imipenem and cilastatin were determined by high-performance liquid chromatography. Pharmacokinetic variables were calculated by a first-order, two-compartment pharmacokinetic model for both substances. Total clearances of imipenem and cilastatin (mean ؎ standard deviations) were 122.2 ؎ 28.6 and 29.2 ؎ 13.7 ml/min, respectively, with hemofiltration clearances of 22.9 ؎ 2.5 and 16.1 ؎ 3.1 ml/min, respectively, and nonrenal, nonhemofiltration clearances of 90.8 ؎ 26.3 and 13.2 ؎ 13.9 ml/min, respectively. Mean imipenem dosage requirements were approximately 2,000 mg/24 h (2,111.8 ؎ 493.4 mg/24 h). They were calculated in order to achieve an average steady-state concentration of 12 mg/liter to ensure that concentrations in plasma exceeded the MICs at which 90% of intermediately resistent bacteria are inhibited (8 mg/liter) during the majority of the dosing interval. By contrast, the recommended dosage for patients with end-stage renal failure (ESRF) and infections caused by intermediately resistant bacteria is 1,000 mg/24 h. This remarkable difference may be due (i) to differences in the nonrenal clearance of imipenem between patients with ARF and ESRF and (ii) to the additional clearance by the hemofilter. Since the total clearance of cilastatin was low, marked accumulation occurred, and this was particularly pronounced in patients with additional liver dysfunction. Thus, in patients with ARF managed by CVVH, rather high imipenem doses are required, and these inevitably result in a marked accumulation of cilastatin. The doses of imipenem recommended for patients with ESRF, however, will lead to underdosing and inadequate antibiotic therapy.

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confidence: 99%

Pharmacokinetics of imipenem-cilastatin in critically ill patients undergoing continuous venovenous hemofiltration

Tegeder

Bremer

Oelkers

et al. 1997

Antimicrob Agents Chemother

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“…Imipenem and cilastatin pharmacokinetics were similar in both elderly and young patients with mild renal failure. The elimination constant (ke), CL and AVC were significantly correlated with GFR but not with age (Finch et al 1986). The elimination constant (ke), CL and AVC were significantly correlated with GFR but not with age (Finch et al 1986).…”

Section: Carbapenemsmentioning

confidence: 96%

“…The pharmacokinetics of single and multiple doses of imipenem and cilastatin (each SOOmg 4 times daily for 6 days) in healthy elderly men were studied by Toon et al (1987) and Finch et al (1986). Imipenem and cilastatin pharmacokinetics were similar in both elderly and young patients with mild renal failure.…”

Section: Carbapenemsmentioning

confidence: 99%

Clinical Pharmacokinetics of Antibacterial Drugs in the Elderly

Meyers

Wilkinson

1989

Clinical Pharmacokinetics

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A review of the clinical pharmacokinetics of antibiotics in the healthy elderly reveals that for most compounds a decrease occurs in renal clearance (associated with age-related decreases in renal function), as well as a prolonged half-life and increased area under the plasma concentration-time curve. These changes are amplified in the sick infected elderly. It is important that the treating physician be aware of the potential side-effects of antimicrobial agents, and whenever possible choose those which are associated with the least adverse effects. Individual patient variability, including underlying diseases and other prescribed medications, must be taken into account when dosage is selected. beta-Lactam compounds have a remarkable safety record: specifically in the elderly, their therapeutic/toxic ratio is much higher than that observed with aminoglycosides. Regimens for this class of drugs in the elderly should maintain antibiotic concentrations above the minimum inhibitory concentrations for maximum efficacy. In the treatment of elderly patients, it is suggested that dosage and interval be based on estimated or measured creatinine clearance. Usually, for drugs that are excreted primarily by the kidney (i.e. amino-glycosides, beta-lactams and quinolones), dosage intervals must be increased when there is an associated fall in creatinine clearance. The pharmacokinetic parameters suggest that as an alternative to increasing dosage interval the usual dose may be decreased, but further studies are necessary for confirmation.

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“…Only 11 (36.7%) studies clearly described the specific body weight descriptor used to determine the dose of antimicrobials or to calculate the PK parameters. In the results section, three requirements are reported by at least 90% of studies: (1) reporting the variables that may influence PK variabilities Studies included in the final PK comparison were on meropenem [39][40][41][42][43][44], imipenem [45][46][47][48][49][50], doripenem [51][52][53][54][55][56], linezolid [57][58][59][60][61][62], and vancomycin [63][64][65][66][67][68] (Table 1). Population PK studies in this systematic review identified body weight as a significant determinant of V d for hydrophilic antimicrobials, including meropenem [42,43], imipenem [50], doripenem [51,55,56], linezolid [59,62], and vancomycin [63,66,68].…”

Section: Study Selectionmentioning

confidence: 99%

A Systematic Review on Antimicrobial Pharmacokinetic Differences between Asian and Non-Asian Adult Populations

et al. 2023

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While the relevance of inter-ethnic differences to the pharmacokinetic variabilities of antimicrobials has been reported in studies recruiting healthy subjects, differences in antimicrobial pharmacokinetics between Asian and non-Asian patients with severe pathologic conditions require further investigation. For the purpose of describing the potential differences in antimicrobial pharmacokinetics between Asian and non-Asian populations, a systematic review was performed using six journal databases and six theses/dissertation databases (PROSPERO record CRD42018090054). The pharmacokinetic data of healthy volunteers and non-critically ill and critically ill patients were reviewed. Thirty studies on meropenem, imipenem, doripenem, linezolid, and vancomycin were included in the final descriptive summaries. In studies recruiting hospitalised patients, inconsistent differences in the volume of distribution (Vd) and drug clearance (CL) of the studied antimicrobials between Asian and non-Asian patients were observed. Additionally, factors other than ethnicity, such as demographic (e.g., age) or clinical (e.g., sepsis) factors, were suggested to better characterise these pharmacokinetic differences. Inconsistent differences in pharmacokinetic parameters between Asian and non-Asian subjects/patients may suggest that ethnicity is not an important predictor to characterise interindividual pharmacokinetic differences between meropenem, imipenem, doripenem, linezolid, and vancomycin. Therefore, the dosing regimens of these antimicrobials should be adjusted according to patients’ demographic or clinical characteristics that can better describe pharmacokinetic differences.

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Pharmacokinetic studies of imipenem/cilastatin in elderly patients

Cited by 8 publications

References 0 publications

Pharmacokinetics of imipenem-cilastatin in critically ill patients undergoing continuous venovenous hemofiltration

Pharmacokinetics of imipenem-cilastatin in critically ill patients undergoing continuous venovenous hemofiltration

Clinical Pharmacokinetics of Antibacterial Drugs in the Elderly

A Systematic Review on Antimicrobial Pharmacokinetic Differences between Asian and Non-Asian Adult Populations

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