| Autor: |
Abolhassani-Chimeh R; University Medical Center Groningengrid.4494.d, Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands., Akkerman OW; University Medical Center Groningengrid.4494.d, Department of Pulmonary Diseases, University of Groningen, Groningen, the Netherlands.; University Medical Center Groningengrid.4494.d, Tuberculosis Center Beatrixoord, University of Groningen, Haren, the Netherlands., Saktiawati AMI; Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.; Center for Tropical Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia., Punt NC; University Medical Center Groningengrid.4494.d, Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands.; Medimatics, Maastricht, the Netherlands., Bolhuis MS; University Medical Center Groningengrid.4494.d, Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands., Subronto YW; Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia., Sumardi; Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia., van der Werf TS; University Medical Center Groningengrid.4494.d, Department of Pulmonary Diseases, University of Groningen, Groningen, the Netherlands.; University Medical Center Groningengrid.4494.d, Department of Internal Medicine/Infectious Diseases, University of Groningen, Groningen, the Netherlands., Kosterink JGW; University Medical Center Groningengrid.4494.d, Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands.; Pharmacotherapy, Epidemiology and Economy, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands., Alffenaar JC; University Medical Center Groningengrid.4494.d, Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands.; Faculty of Medicine and Health, School of Pharmacy, University of Sydney, Sydney, New South Wales, Australia.; Westmead Hospital, Westmead, New South Wales, Australia.; Marie Bashir Institute of Infectious Diseases and Biosecurity, University of Sydney, Sydney, New South Wales, Australia., Sturkenboom MGG; University Medical Center Groningengrid.4494.d, Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands. |
| Abstrakt: |
Pyrazinamide is one of the first-line antituberculosis drugs. The efficacy of pyrazinamide is associated with the ratio of 24-h area under the concentration-time curve (AUC 24 ) to MIC. The objective of this study was to develop and validate a limited sampling strategy (LSS) based on a population pharmacokinetic (popPK) model to predict AUC 24 . A popPK model was developed using an iterative two-stage Bayesian procedure and was externally validated. Using data from 20 treatment-naive adult tuberculosis (TB) patients, a one compartment model with transit absorption and first-order elimination best described pyrazinamide pharmacokinetics and fed state was the only significant covariate for absorption rate constant (k a ). External validation, using data from 26 TB patients, showed that the popPK model predicted AUC 24 with a slight underestimation of 2.1%. LSS were calculated using Monte Carlo simulation ( n = 10,000). External validation showed LSS with time points 0 h, 2 h, and 6 h performed best with RMSE of 9.90% and bias of 0.06%. Food slowed absorption of pyrazinamide, but did not affect bioavailability, which may be advantageous in case of nausea or vomiting in which food can be used to diminish these effects. In this study, we successfully developed and validated a popPK model and LSS, using 0 h, 2 h, and 6 h postdose samples, that could be used to perform therapeutic drug monitoring (TDM) of pyrazinamide in TB patients. |
