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Modeling of trough plasma bismuth concentrations
J E Bennett1, J C Wakefield, L F Lacey
1Department of Mathematics, Imperial College, London, United Kingdom.
Journal of Pharmacokinetics and Biopharmaceutics
|February 1, 1997
Summary
Pharmacokinetics of bismuth from ranitidine bismuth citrate are complex. This study developed a simplified model using Bayesian analysis, identifying clarithromycin and creatinine clearance as key influences on bismuth levels in patients.
Area of Science:
- Pharmacology
- Drug Metabolism
- Clinical Pharmacokinetics
Background:
- Oral ranitidine bismuth citrate exhibits complex and variable bismuth disposition pharmacokinetics.
- Previous volunteer studies suggested a three-compartment model with first-order absorption for bismuth.
Purpose of the Study:
- To develop a reliable pharmacokinetic model for bismuth in patients using a reduced model and Bayesian techniques.
- To identify covariates influencing bismuth trough concentrations in patients undergoing long-term treatment.
Main Methods:
- Bayesian sampling techniques were employed to analyze pooled patient data (1140 trough concentrations from 802 patients).
- A reduced pharmacokinetic model with an informative prior derived from volunteer data was utilized.
- Predictive distributions were used for diagnostics and inference, including Cmax, Cmin, and AUC.
Main Results:
- Bismuth trough concentrations were significantly influenced by the coadministration of clarithromycin.
- Creatinine clearance was identified as another significant covariate affecting bismuth levels.
- A simulation study validated the estimates obtained from the reduced model.
Conclusions:
- A simplified Bayesian pharmacokinetic model effectively describes bismuth disposition in patients treated with ranitidine bismuth citrate.
- Clarithromycin and creatinine clearance are important factors to consider in managing bismuth therapy.
- The model allows for the prediction of pharmacokinetic characteristics in new individuals.