Mwlod Ghareeb1, Reginald Y Gohh2, Fatemeh Akhlaghi3. 1. Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, 495A College of Pharmacy, 7 Greenhouse Road, Kingston, RI, 02881, USA. 2. Division of Organ Transplantation, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA. 3. Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, 495A College of Pharmacy, 7 Greenhouse Road, Kingston, RI, 02881, USA. fatemeh@uri.edu.
Abstract
OBJECTIVE: The objective of this study was to examine the association between tacrolimus concentration in oral fluids and in whole blood and to investigate the various factors that influence this relationship. PATIENTS AND METHODS: Forty-six adult kidney transplant recipients were included in the study. Study A (ten patients) included the collection of several paired oral fluid samples by passive drool over a 12-h post-dose period. Study B (36 patients) included the collection of oral fluids pre-dose and at 2 h after the tacrolimus dose under three conditions: un-stimulated, after stimulation with a tart candy, and after mouth rinsing. The tacrolimus concentration in oral fluids was measured by a specially developed sensitive and specific liquid chromatography mass spectrometry method. A salivary transferrin concentration of >1 mg/dL was used as a cut-off value for oral fluid blood contamination. RESULTS: Rinsing the oral cavity before sampling proved to provide the most suitable sampling strategy giving a correlation coefficient value of 0.71 (p = 0.001) between the tacrolimus concentration in oral fluids and the tacrolimus concentration in whole blood at trough. Mean and 95% confidence interval of tacrolimus concentration in oral fluids at the pre-dose concentration for samples collected after mouth rinsing was 584 (436, 782) pg/mL. The ratio of the tacrolimus concentration in oral fluids to the tacrolimus concentration in whole blood (*100) was 11% (95% confidence interval 9-13) for all sampling times. Oral fluid pH or weight of a saliva sample did not influence the tacrolimus concentration in oral fluids. Tacrolimus distribution into oral fluids exhibited a delay with a pronounced counter-clockwise hysteresis with respect to the time after dose. A multivariate analysis of variance revealed that the tacrolimus concentration in oral fluids is related to the tacrolimus concentration in whole blood and tacrolimus plasma-binding proteins including albumin and cholesterol. CONCLUSION: An optimal sampling strategy for the determination of the tacrolimus concentration in oral fluids was established. Measuring the tacrolimus concentration in oral fluids appears to be a feasible and non-invasive method for predicting the concentration of tacrolimus in whole blood.
OBJECTIVE: The objective of this study was to examine the association between tacrolimus concentration in oral fluids and in whole blood and to investigate the various factors that influence this relationship. PATIENTS AND METHODS: Forty-six adult kidney transplant recipients were included in the study. Study A (ten patients) included the collection of several paired oral fluid samples by passive drool over a 12-h post-dose period. Study B (36 patients) included the collection of oral fluids pre-dose and at 2 h after the tacrolimus dose under three conditions: un-stimulated, after stimulation with a tart candy, and after mouth rinsing. The tacrolimus concentration in oral fluids was measured by a specially developed sensitive and specific liquid chromatography mass spectrometry method. A salivary transferrin concentration of >1 mg/dL was used as a cut-off value for oral fluid blood contamination. RESULTS: Rinsing the oral cavity before sampling proved to provide the most suitable sampling strategy giving a correlation coefficient value of 0.71 (p = 0.001) between the tacrolimus concentration in oral fluids and the tacrolimus concentration in whole blood at trough. Mean and 95% confidence interval of tacrolimus concentration in oral fluids at the pre-dose concentration for samples collected after mouth rinsing was 584 (436, 782) pg/mL. The ratio of the tacrolimus concentration in oral fluids to the tacrolimus concentration in whole blood (*100) was 11% (95% confidence interval 9-13) for all sampling times. Oral fluid pH or weight of a saliva sample did not influence the tacrolimus concentration in oral fluids. Tacrolimus distribution into oral fluids exhibited a delay with a pronounced counter-clockwise hysteresis with respect to the time after dose. A multivariate analysis of variance revealed that the tacrolimus concentration in oral fluids is related to the tacrolimus concentration in whole blood and tacrolimus plasma-binding proteins including albumin and cholesterol. CONCLUSION: An optimal sampling strategy for the determination of the tacrolimus concentration in oral fluids was established. Measuring the tacrolimus concentration in oral fluids appears to be a feasible and non-invasive method for predicting the concentration of tacrolimus in whole blood.
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