TY - JOUR
T1 - Influence of dissolution rate and pH of oral medications on drug-induced esophageal injury
AU - Bailey, Robert T.
AU - Bonavina, Luigi
AU - Nwakama, Patrick E.
AU - Demeester, Tom R.
AU - Cheng, Shih Chuan
N1 - Funding Information:
Bailey Robert T. Jr. Bonavina Luigi Nwakama Patrick E. DeMeester Tom R. Cheng Shih-Chuan ROBERT T. BAILEY, Jr. , Pharm.D., is an Associate Professor of Surgery and Pharmacy, and the Director of Surgical Research and Development, Department of Surgery, Creighton University, Suite 3740, 601 N. 30th Street, Omaha, NE 68131; LUIGI BONAVINA , M.D., is an Assistant Professor, Department of Surgery, University of Padova Medical School, Italy; PATRICK E. NWAKAMA , Pharm.D., is a Clinical Assistant Professor of Pharmacy, Department of Clinical Pharmacy, University of Maryland, and Assistant Director of Clinical Services, St. Joseph Hospital, Baltimore, MD; TOM R. DEMEESTER , M.D., is a Professor and the Chairman, Department of Surgery; and SHIH-CHUAN CHENG , Ph.D., is an Associate Professor of Mathematics and Surgery, Department of Mathematics and Computer Science, Creighton University, Omaha, NE. Reprints: Robert T. Bailey, Jr., Pharm.D., Director of Surgical Research and Development, Department of Surgery, Creighton University, Suite 3740, 601 N. 30th Street, Omaha, NE 68131 6 1990 24 6 571 574 © 1990 SAGE Publications 1990 SAGE Publications The in vitro dissolution time and pH were measured for 16 drug products in capsule or tablet form representative of oral medications known to cause esophageal injury. The test drugs included Vibramycin, Minocin, quinidine sulfate, Cleocin HCl, Indocin, Tolectin 200, ferrous sulfate, vitamin C, aspirin, Procardia, phenobarbital, Dilantin, Butazolidin, Noctec, K-Dur, and Quinaglute. Artificial saliva (10 mL) was placed in a small beaker along with a pH probe connected to a digital display pH meter and a strip—chart recorder. The salivary pH was measured at baseline and continuously during the dissolution of each test medication and the time taken for complete dissolution was recorded. This experiment was repeated six times for each drug. Baseline and final dissolution pH were compared statistically for differences using the Wilcoxon matched-pairs signed-ranks test. Significance was established at the 0.05 level. Only three medications tested (vitamin C, aspirin, and Dilantin) produced a dissolution pH outside the range of physiological esophageal pH values. Although the majority of the test drugs significantly altered the baseline pH, the final dissolution pH did not fall outside the physiologic range. Nine of the 16 test drugs dissolved completely within 10 minutes, whereas the remaining 7 drugs took 30 minutes or longer (up to 24 hours) to dissolve. We conclude that the dissolution pH of potentially caustic medications does not appear to be a primary mechanism of drug-induced esophageal injury, whereas a rapid dissolution rate may play an important role in the pathogenesis of the lesion. Más de 300 casos de lesiones esofágicas atribuidas a la ingestión de medicamentos han sido reportados en la literatura desde el año 1970. La mayoría de estas lesiones se curan espontáneamente; sin embargo, algunas se complican seriamente ocasionando ulceración esofágica, estrechez, hemorragia, perforación, e inclusive muerte. El mecanismo por el cual estas lesiones ocurren no está completamente elucidado. Factores tales como la velocidad de disolución del medicamento, la osmolaridad y la toxicidad química intrínsica del medicamento han sido involucrados en la patogénesis de la lesión esofágica; se carece, sin embargo, de información objectiva que sustente estas teorías. Este estudio tuvo como objetivo determinar la velocidad de disolución in vitro y el pH de algunos de los medicamentos orales comúnmente prescritos e implicados en el daño esofágico. Los medicamentos estudiados fueron: Vibramycin, Minocin, sulfato de quinidina, Cleocin, Indocin, Tolectin, sulfato ferroso, vitamina C, aspirina, Procardia, fenobarbital, Dilantin, Butazolidin, Noctec, K-Dur, y Quinaglute. Diez mL de saliva artificial fueron colocados en un vaso de precipitados pequeño conectado a un medidor de pH de lectura digital y a un registrador gráfico de cinta. Se midió el pH salival basal y el pH durante la disolución de cada medicamento en estudio; también se midió el tiempo requerido para la disolución total del medicamento. El experimento fue repetido seis veces por cada medicamento. Los pHs basales y los obtenidos al final de la disolución fueron comparados estadísticamente para determinar si había diferencias significativas. Esto se llevó a cabo usando el método no paramétrico conocido como Wilcoxon matched-pairs signed-ranks test. El nivel de significancia fue establecido en 0.05. Sólo tres de los medicamentos estudiados (la vitamina C, la aspirina, y el Dilatin) produjeron un pH de disolución fuera del rango fisiológico de valores de pH esofágico. Aunque la mayoría de los medicamentos estudiados modificaron significativamente el pH basal, el pH de disolución final no cayó fuera del rango fisiológico. Nueve de los 16 medicamentos estudiados se disolvieron completamente en más de diez minutos, mientras que los siete restantes se disolvieron en 30 o más minutos (hasta en 24 horas). Se concluye que el pH de disolución de medicamentos potencialmente cáusticos no parece estar involucrado en el mecanismo de daño esofágico. Sin embargo, se piensa que la velocidad de disolución rápida puede jugar un papel importante en la patogénesis de la lesión. Le pH et le temps de dissolution de 16 médicaments reconnus comme pouvant endommager l'oesophage ont été mesurés in vitro. Il s'agit du Vibramycin, Minocin, sulfate de quinidine, Cleocin, Indocin, Tolectin, sulfate ferreux, vitamine C, aspirine, Procardia, phénobarbital, Dilantin, Butazolidin, Noctec, K-Dur et Quinaglute. Le pH salivaire était mesuré au temps zéro, puis continuellement durant la dissolution de chaque médicament. Le temps nécessaire pour atteindre une dissolution complète était aussi enregistré. L'expérimentation était répétée six fois pour chacun des produits. La valeur du pH au temps zéro était comparée à celle obtenue en fin de dissolution. La majorité des produits altéraient significativement le pH. Cependant, le pH obtenu en fin de dissolution demeurait dans l'intervalle physiologique. La vitamine C, l'aspirine, et le Dilantin ont produit un pH de dissolution dépassant l'intervalle des valeurs physiologiques du pH oesophagien. Neuf des 16 médicaments observés se dissolvaient complètement en dix minutes. Les sept autres médicaments se dissolvaient en 30 minutes ou plus. Les auteurs concluent que le pH de dissolution de ces médicaments reconnus comme potentiellement caustique, n'apparaît pas être le mécanisme d'induction principal des lésions oesophagiennes, alors qu'un taux de dissolution rapide pourrait jouer un rôle important dans la pathogénèse des lésions.
PY - 1990/6
Y1 - 1990/6
N2 - The in vitro dissolution time and pH were measured for 16 drug products in capsule or tablet form representative of oral medications known to cause esophageal injury. The test drugs included Vibramycin, Minocin, quinidine sulfate, Cleocin HCl, Indocin, Tolectin 200, ferrous sulfate, vitamin C, aspirin, Procardia, phenobarbital, Dilantin, Butazolidin, Noctec, K-Dur, and Quinaglute. Artificial saliva (10 mL) was placed in a small beaker along with a pH probe connected to a digital display pH meter and a strip—chart recorder. The salivary pH was measured at baseline and continuously during the dissolution of each test medication and the time taken for complete dissolution was recorded. This experiment was repeated six times for each drug. Baseline and final dissolution pH were compared statistically for differences using the Wilcoxon matched-pairs signed-ranks test. Significance was established at the 0.05 level. Only three medications tested (vitamin C, aspirin, and Dilantin) produced a dissolution pH outside the range of physiological esophageal pH values. Although the majority of the test drugs significantly altered the baseline pH, the final dissolution pH did not fall outside the physiologic range. Nine of the 16 test drugs dissolved completely within 10 minutes, whereas the remaining 7 drugs took 30 minutes or longer (up to 24 hours) to dissolve. We conclude that the dissolution pH of potentially caustic medications does not appear to be a primary mechanism of drug-induced esophageal injury, whereas a rapid dissolution rate may play an important role in the pathogenesis of the lesion.
AB - The in vitro dissolution time and pH were measured for 16 drug products in capsule or tablet form representative of oral medications known to cause esophageal injury. The test drugs included Vibramycin, Minocin, quinidine sulfate, Cleocin HCl, Indocin, Tolectin 200, ferrous sulfate, vitamin C, aspirin, Procardia, phenobarbital, Dilantin, Butazolidin, Noctec, K-Dur, and Quinaglute. Artificial saliva (10 mL) was placed in a small beaker along with a pH probe connected to a digital display pH meter and a strip—chart recorder. The salivary pH was measured at baseline and continuously during the dissolution of each test medication and the time taken for complete dissolution was recorded. This experiment was repeated six times for each drug. Baseline and final dissolution pH were compared statistically for differences using the Wilcoxon matched-pairs signed-ranks test. Significance was established at the 0.05 level. Only three medications tested (vitamin C, aspirin, and Dilantin) produced a dissolution pH outside the range of physiological esophageal pH values. Although the majority of the test drugs significantly altered the baseline pH, the final dissolution pH did not fall outside the physiologic range. Nine of the 16 test drugs dissolved completely within 10 minutes, whereas the remaining 7 drugs took 30 minutes or longer (up to 24 hours) to dissolve. We conclude that the dissolution pH of potentially caustic medications does not appear to be a primary mechanism of drug-induced esophageal injury, whereas a rapid dissolution rate may play an important role in the pathogenesis of the lesion.
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U2 - 10.1177/106002809002400601
DO - 10.1177/106002809002400601
M3 - Article
C2 - 2360332
AN - SCOPUS:0025368994
VL - 24
SP - 571
EP - 574
JO - Annals of Pharmacotherapy
JF - Annals of Pharmacotherapy
SN - 1060-0280
IS - 6
ER -