Dataset Information

CYP3A activity in severe liver cirrhosis correlates with Child-Pugh and model for end-stage liver disease (MELD) scores.

ABSTRACT:

Aims

Impaired liver function often necessitates drug dose adjustment to avoid excessive drug accumulation and adverse events, but a marker for the extent of the required adjustment is lacking. The aim of this study was to investigate whether Child-Pugh (CP) and model for end-stage liver disease (MELD) scores correlate with drug clearance.

Methods

Midazolam was used as a CYP3A probe and its pharmacokinetics were analyzed in 24 patients with mild to severe liver cirrhosis (n = 4, 10 and 10 with CP class A, B and C, respectively) and six patients without liver disease.

Results

Both scores correlated well with unbound midazolam clearance (CLu ), unbound midazolam fraction and half-life (all P < 0.01), whereas the unbound steady-state volume of distribution was not significantly changed. In patients with severe liver cirrhosis unbound midazolam clearance was only 14% of controls (CP C: CLu = 843 ± 346 l? h(-1), MELD ? 15: CLu = 805 ± 474?l? h(-1), controls: CLu = 5815 ± 2649?l? h(-1), P < 0.01).

Conclusion

The correlation with unbound midazolam clearance suggests that either score predicts the metabolic capacity of CYP3A, the most relevant drug metabolizing enzyme subfamily in humans.

SUBMITTER: Albarmawi A

PROVIDER: S-EPMC3895357 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Publications

CYP3A activity in severe liver cirrhosis correlates with Child-Pugh and model for end-stage liver disease (MELD) scores.

Albarmawi Albader A Czock David D Gauss Annika A Ehehalt Robert R Lorenzo Bermejo Justo J Burhenne Jürgen J Ganten Tom M TM Sauer Peter P Haefeli Walter E WE

British journal of clinical pharmacology 20140101 1

<h4>Aims</h4>Impaired liver function often necessitates drug dose adjustment to avoid excessive drug accumulation and adverse events, but a marker for the extent of the required adjustment is lacking. The aim of this study was to investigate whether Child-Pugh (CP) and model for end-stage liver disease (MELD) scores correlate with drug clearance.<h4>Methods</h4>Midazolam was used as a CYP3A probe and its pharmacokinetics were analyzed in 24 patients with mild to severe liver cirrhosis (n = 4, 10 ...[more]

PMID: 23772874

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Project description:Background and Aim. Various methods, including the Child-Pugh score, the model for end-stage liver disease (MELD) score, the MELD combined with serum sodium concentration (MELD-Na) score, the integrated MELD (iMELD) score, and the albumin-bilirubin (ALBI) score, have been widely used for predicting the survival of decompensated cirrhosis (DeCi) patients. In this study, we defined and compared the prognostic value of these scores to predict mortality in DeCi patients.MethodsWe performed a single-center, observational retrospective study and analyzed 456 DeCi patients who were hospitalized in the gastroenterology department. The biochemical examination results and demographic characteristics of the patients were obtained, and five scores were calculated upon admission after 24 hours. All patients were observed until death, loss to follow-up, or specific follow-up times (28 days, 90 days, and 6 months). A receiver operating characteristic (ROC) curve was used to evaluate the ability of these methods to predict mortality in DeCi patients.ResultsAt 28 days, 90 days, and 6 months, the cumulative number of deaths was 50 (11.0%), 76 (16.6%), and 91 (19.9%), respectively. The scores were significantly higher in nonsurviving patients than in surviving patients. All scores yielded viable values in predicting 28-day, 90-day, and 6-month prognoses for DeCi patients. The areas under the ROC curve (AUROCs) of the ALBI score were higher than those of the other scores, which were only over 0.700 at 28 days. The AUROC of the MELD score was higher than that of the other scores, including the MELD-Na and iMELD scores, at 90 days and 6 months.ConclusionAll five methods (Child-Pugh score, MELD score, MELD-Na score, iMELD score, and ALBI score) provided a reliable prediction of mortality for both the short-term and long-term prognosis of patients with DeCi. The ALBI score may be particularly useful for assessing short-term outcomes, whereas the MELD score may be particularly useful for assessing long-term outcomes.

Dataset Information

CYP3A activity in severe liver cirrhosis correlates with Child-Pugh and model for end-stage liver disease (MELD) scores.

Aims

Methods

Results

Conclusion

Publications

CYP3A activity in severe liver cirrhosis correlates with Child-Pugh and model for end-stage liver disease (MELD) scores.

Similar Datasets

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