This study aimed to define the pharmacokinetics (PKs) of oral mannitol used as an osmotic laxative for bowel preparation for colonoscopy. The PKs of oral mannitol was evaluated in a substudy as part of a phase II dose-finding, international, multicenter, randomized, parallel-group, endoscopist-blinded study. Patients were randomly assigned to take 50, 100, or 150 g mannitol. Venous blood samples were drawn at baseline (T0), 1 h (T1), 2 h (T2), 4 h (T4), and 8 h (T8) after completion of mannitol self-administration. The mean mannitol plasma concentrations (mg/ml) were dose-dependent with a consistent difference among doses. The mean maximum concentration (Cmax) ± SD was 0.63 ± 0.15, 1.02 ± 0.28, and 1.36 ± 0.39 mg/ml, in the three dosage groups, respectively. The mean area under the curve from zero to infinity (AUC0−∞) was 2.667 ± 0.668, 4.992 ± 1.706, and 7.403 ± 3.472 mg/ml*h in the 50, 100, and 150 g mannitol dose groups, respectively. Bioavailability was similar in the three dose groups and was just over 20% (0.243 ± 0.073, 0.209 ± 0.081, and 0.228 ± 0.093 in the 50, 100, and 150 g mannitol dose groups, respectively). The present study showed that the bioavailability of oral mannitol is just over 20% and is similar for the three tested doses (50, 100, and 150 g). The linear increase in Cmax, AUC0−t8, and AUC0−∞ must be considered when choosing the oral mannitol dose for bowel preparation to avoid its systemic osmotic effects.
Fiori, G., Spada, C., Soru, P., Tontini, G. E., Bravi, I., Cesana, B. M., Cesaro, P., Manes, G., Orsatti, A., Prada, A., Quadarella, A., Schettino, M., Spina, L., Trovato, C., Carnovali, M., Vecchi, M., Cavallaro, F., Codazzi, M., De Nucci, G., De Roberto, G., Devani, M., Di Paolo, D., Elli, L., Hinkel, C., Jakobs, R., Janke, D., Lombardo, V., Lovera, M., Radaelli, F., Ravizza, D., Uebel, P., Valats, J. C., Vollmar, J., Zimmermann, T. A., Ciprandi, G., Pharmacokinetics of oral mannitol for bowel preparation for colonoscopy, <<CLINICAL AND TRANSLATIONAL SCIENCE>>, 2022; 15 (10): 2448-2457. [doi:10.1111/cts.13373] [https://hdl.handle.net/10807/250881]
Pharmacokinetics of oral mannitol for bowel preparation for colonoscopy
Spada, Cristiano;Cesana, Bruno Mario;Cesaro, Paola;Quadarella, Alessandro;Cavallaro, Fabio;Lovera, Mauro;Zimmermann, Thomas Alexander;Ciprandi, Guido
2022
Abstract
This study aimed to define the pharmacokinetics (PKs) of oral mannitol used as an osmotic laxative for bowel preparation for colonoscopy. The PKs of oral mannitol was evaluated in a substudy as part of a phase II dose-finding, international, multicenter, randomized, parallel-group, endoscopist-blinded study. Patients were randomly assigned to take 50, 100, or 150 g mannitol. Venous blood samples were drawn at baseline (T0), 1 h (T1), 2 h (T2), 4 h (T4), and 8 h (T8) after completion of mannitol self-administration. The mean mannitol plasma concentrations (mg/ml) were dose-dependent with a consistent difference among doses. The mean maximum concentration (Cmax) ± SD was 0.63 ± 0.15, 1.02 ± 0.28, and 1.36 ± 0.39 mg/ml, in the three dosage groups, respectively. The mean area under the curve from zero to infinity (AUC0−∞) was 2.667 ± 0.668, 4.992 ± 1.706, and 7.403 ± 3.472 mg/ml*h in the 50, 100, and 150 g mannitol dose groups, respectively. Bioavailability was similar in the three dose groups and was just over 20% (0.243 ± 0.073, 0.209 ± 0.081, and 0.228 ± 0.093 in the 50, 100, and 150 g mannitol dose groups, respectively). The present study showed that the bioavailability of oral mannitol is just over 20% and is similar for the three tested doses (50, 100, and 150 g). The linear increase in Cmax, AUC0−t8, and AUC0−∞ must be considered when choosing the oral mannitol dose for bowel preparation to avoid its systemic osmotic effects.
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