Population pharmacokinetics of lorazepam and midazolam and their metabolites in intensive care patients on continuous venovenous hemofiltration

Swart, Eleonora L.; Jongh, Joost de; Zuideveld, Klaas P.; Danhof, Meindert; Thijs, L. G.; Schijndel, Robert J.M. Strack van

doi:10.1053/j.ajkd.2004.09.004

Cited by 47 publications

(36 citation statements)

References 25 publications

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“…Our finding for midazolam clearance (population mean: 8.42 l h −1 ) is in agreement with previous studies in critically ill patients . It is also comparable to the estimated clearance found in a recent study in critically ill children where they also found an effect of inflammation (to compare these values, the results of Vet et al were adapted to values for a 70 kg individual) .…”

Section: Discussionsupporting

confidence: 92%

Hypoalbuminaemia and decreased midazolam clearance in terminally ill adult patients, an inflammatory effect?

Franken

Masman

Winter

et al. 2017

Brit J Clinical Pharma

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Aims Midazolam is the drug of choice for palliative sedation and is titrated to achieve the desired level of sedation. Because of large inter‐individual variability (IIV), however, the time it takes to achieve adequate sedation varies widely. It would therefore greatly improve clinical care if an individualized dose could be determined beforehand. To find clinically relevant parameters for dose individualization, we performed a pharmacokinetic study on midazolam, 1OH‐midazolam (1‐OH‐M) and 1OH‐midazolam‐glucuronide (1‐OH‐MG) in terminally ill patients. Methods Using nonlinear mixed effects modelling (NONMEM 7.2), a population pharmacokinetic analysis was conducted with 192 samples from 45 terminally ill patients who received midazolam either orally or subcutaneously. The covariates analysed were patient characteristics, co‐medication and blood chemistry levels. Results The data were accurately described by a one compartment model for midazolam, 1‐OH‐M and 1‐OH‐MG. The population mean estimates for midazolam, 1‐OH‐M and 1‐OH‐MG clearance were 8.4 l h−1 (RSE 9%, IIV 49%), 45.4 l h−1 (RSE 12%, IIV 60.5%) and 5.1 l h−1 (RSE 11%, IIV 49.9%), respectively. 1‐OH‐MG clearance was correlated with the estimated glomular filtration rate (eGFR) explaining 28.4% of the IIV in 1‐OH‐MG clearance. In addition, low albumin levels were associated with decreased midazolam clearance, explaining 18.2% of the IIV. Conclusion Our study indicates albumin levels and eGFR as relevant clinical parameters to optimize midazolam dosing in terminally ill patients. The correlation between low albumin levels and decreased midazolam clearance is probably a result of inflammatory response as high CRP levels were correlated in a similar way.

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Section: Discussionsupporting

confidence: 92%

Hypoalbuminaemia and decreased midazolam clearance in terminally ill adult patients, an inflammatory effect?

Franken

Masman

Winter

et al. 2017

Brit J Clinical Pharma

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“…Benzodiazepine clearance is reduced in patients with hepatic dysfunction and other disease states, in elderly patients, and when administered with other medications that inhibit cytochrome P 450 enzyme systems and/or glucuronide conjugation in the liver (173)(174)(175). Benzodiazepine clearance is reduced in patients with hepatic dysfunction and other disease states, in elderly patients, and when administered with other medications that inhibit cytochrome P 450 enzyme systems and/or glucuronide conjugation in the liver (173)(174)(175).…”

Section: Agitation and Sedationmentioning

confidence: 99%

Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit

Barr

Fraser

Puntillo

et al. 2013

Critical Care Medicine

3,074

3,013

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“…CVVH fluid is an aqueous substance with electrolytes and is used in continuous veno-venous hemofiltration (CVVH) as a replacement therapy in case of acute renal failure [11,12]. With reference to the analysis in human plasma, the validation of PG analysis in CVVH fluid resulted in equal or better values for the mentioned validation parameters.…”

Section: Validationmentioning

confidence: 99%

LC Determination of Propylene Glycol in Human Plasma After Pre-Column Derivatization with Benzoyl Chloride

Sinjewel

Swart

Lingeman

et al. 2007

Chroma

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A simple high-performance liquid chromatographic method, using photodiode array detection was developed for the determination of propylene glycol in human plasma and in the fluid retreived after continuous veno-venous hemofiltration. The method entailed alkaline derivatization with benzoyl chloride and ethylene glycol as internal standard. The separation of the compounds, after extraction with pentane, was carried out on a Pursuit C8 column with UVdetection at 230 nm. Validation samples were analyzed with an accuracy between 95 and 105%, and intra-and inter-day coefficients of variation of less than 8%. The calibration curve was linear over a concentration range of 5-100 mg L )1 with a detection limit of 1 mg L )1. Blood plasma samples of several patients were analysed by using the prescribed method with propylene glycol concentrations varying from 5 to 98 mg L )1 . Compared to previously described LC methods, this method is ten times more sensitive and thus suitable for use in pharmacokinetic studies of propylene glycol.

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Population pharmacokinetics of lorazepam and midazolam and their metabolites in intensive care patients on continuous venovenous hemofiltration

Cited by 47 publications

References 25 publications

Hypoalbuminaemia and decreased midazolam clearance in terminally ill adult patients, an inflammatory effect?

Hypoalbuminaemia and decreased midazolam clearance in terminally ill adult patients, an inflammatory effect?

Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit

LC Determination of Propylene Glycol in Human Plasma After Pre-Column Derivatization with Benzoyl Chloride

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