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Influence of concentration‐dependent protein binding on serum concentrations and urinary excretion of disopyramide and its metabolite following oral administration
Author(s) -
Haughey David B.,
Lima John J.
Publication year - 1983
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510040202
Subject(s) - disopyramide , metabolite , urine , free fraction , pharmacokinetics , chemistry , excretion , endocrinology , serum concentration , medicine , renal function , oral administration , urinary system , renal physiology , volunteer , pharmacology , biology , agronomy
Concentrations of disopyramide (D) and mono‐N‐dealkyldisopyramide (MND) were measured in serum and urine following administration of 100, 150, 200, and 300 mg D to four volunteers. The free fraction of D in serum was drug concentration‐dependent in all four subjects following the administration of the four doses. Areas under the free (unbound) D serum concentration‐time curves (AUC 0–9 free ) were linearly related to dose following 100–200 mg D. AUC 0–9 freevalues were 30–60 per cent higher than expected in two subjects following 300 mg D due to an apparent dose‐dependent decrease in D renal tubular secretion. Renal clearance of free D averaged 10·91h −1 . The renal clearance of MND averaged 10·31h −1 . The urinary excretion of MND was proportional to disopyramide dose.