{'fraction_non_alphanumeric': 0.01859628074385123, 'fraction_numerical': 0.007198560287942412, 'mean_word_length': 5.725806451612903, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Pharmacokinetics of Cibenzoline After Single and Repetitive Dosing in Healthy Volunteers

Twenty‐five healthy, adult male volunteers entered two open‐label parallel studies, each designed to define the pharmacokinetics of single and multiple oral doses of cibenzoline. Each volunteer received a single 160‐mg oral dose of cibenzoline followed two or three days later by 160 mg of cibenzoline q12h for seven days. Plasma concentration‐time profiles and urinary excretion rate data were used to determine pharmacokinetic parameters for unchanged drug. The apparent half‐life following administration of the last dose (9.7 hours) was slightly longer than that observed after the first dose (8.4 hours). Total body clearance and nonrenal clearance were decreased after the last dose compared with the first dose, whereas renal clearance was not significantly altered. After both the first and last dose, the renal clearance greatly exceeded the glomerular filtration rate, suggesting that tubular secretion participates in the renal excretion of cibenzoline. Plasma concentrations from samples collected during the multiple‐dose regimen suggest that a slight but statistically significant diurnal variation in the absorption and/or clearance of drug occurred during the course of the study. Overall, the pharmacokinetics of cibenzoline are characterized by a slightly longer half‐life during multiple dosing than that observed following a single dose, due to a decrease in the nonrenal clearance. The multiple‐dose pharmacokinetics reported herein are consistent with bid dosing for the maintenance of therapeutic plasma concentrations in patients taking chronic therapy.