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Correlation of plasma ibuprofen levels with biological activity.

Abstract Investigations with ibuprofen [(±)- p -isobutylhydratropic acid], a well-tolerated, orally active, anti-inflammatory drug, were undertaken to: (a) determine the relationship among plasma drug concentrations, administered dose, and anti-inflammatory activity in developing and established polyarthritis in rats; and (b) compare the plasma drug disappearance half-lives in normal and polyarthritic rats. The results indicated that plasma drug concentrations in normal and polyarthritic rats were dose related. The logarithm of biological activity expressed as [% IPA/(100 – % IPA)], where % IPA is the mean percent inhibition of developing or established polyarthritis as measured by plasma inflammation units, was related to the logarithms of: (a) administered dose (mg kg − 1 ), (b) plasma drug concentrations ( μ g ml − 1 ) at 2 hr postadministration, and (c) average plasma drug concentrations ( μ g ml − 1 ) in a dosage interval at the equilibrium state. Half-lives for elimination of ibuprofen from the plasma of normal rats (after single-dose oral drug administration) and polyarthritic rats (after 29 doses) were essentially identical.