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Oxaprozin Dose Proportionality
Author(s) -
CHIANG SOONG T.,
LASSETER KENNETH C.,
FLUCK EUGENE R.,
JANSSEN FRANK W.,
LEELAVATHI DODDA,
HUBSHER JEROME A.
Publication year - 1984
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1984.tb02761.x
Subject(s) - chemistry , volume of distribution , pharmacokinetics , plasma concentration , crossover study , pharmacology , plasma clearance , oral dose , plasma volume , distribution (mathematics) , medicine , mathematics , mathematical analysis , alternative medicine , pathology , placebo
Twelve normal subjects each received single 300‐, 600‐, and 1200‐mg oral doses of oxaprozin according to a three‐period crossover design. Total drug plasma concentrations did not increase in proportion to the dose administered. Total clearance (Cl o ) and volume of distribution (V d ) increased with dose, though elimination t 1 2 remained unchanged. The fraction of unbound oxaprozin in plasma (f up ) varied linearly with total plasma concentration: it increased from 0.068 per cent at 10 μg/ml to 0.180 per cent at 170 μg/ml. A parameter f̂ up was therefore introduced to express the average degree of unbound drug plasma for a given dose, and to allow the calculation of unbound volume of distribution (V du ) and intrinsic clearance (Cl i ) as if binding were constant. Even though f̂ up increased with dose, the overall binding in the body (f̂ ub ∼0.52 per cent) was relatively stable. Neither V du nor Cl i changed with dose; hence, unbound oxaprozin kinetics can be considered to be linear. Protein binding had no effect on unbound oxaprozin plasma levels within the given dose range, and there was a one‐to‐one proportionality between the dose administered and the unbound drug concentration in plasma.