Pharmacokinetics of ibuprofen enantiomers in dogs

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Abstract
Inversion of inactive (R)‐ibuprofen to active (S)‐ibuprofen has been suggested to occur presystemically only. In order to investigate the site of inversion in dogs we administered both enantiomers either intravenously or intraduodenally (10 mg/kg) to adult, male beagle dogs (n = 3) in a crossover design. Plasma, urine, and bile were collected for up to 6 h and analyzed stereospecifically by HPLC, according to a previously published method. Pharmacokinetic parameters were calculated using a linear computer program. Absorption after intraduodenal administration occurred rapidly, resulting in maximum plasma concentrations 0.2 h after giving the enantiomer. Approximately 70% of the (R)‐enantiomer (according to AUC) was inverted to the S‐enantiomer independent of route of administration. No R‐ibuprofen could be detected in plasma after (S)‐ibuprofen administration. Mean residence time was found to be 2 to 3 times longer for (S)‐than for (R)‐ibuprofen. Total systemic clearance from plasma was twice as high for (R)‐ than for (S)‐ibuprofen. There were no differences between plasma clearances after intravenous and intraduodenal administration. Between 8 and 17% of dose was recovered in bile [especially as free and conjugated (S)‐ibuprofen] and 3–12% in urine [as (S)‐ibuprofen, hydroxy‐ and carboxyibuprofen, free and conjugated forms]. Small amounts of (R)‐ibuprofen were detected in bile after intraduodenal administration of (R)‐ibuprofen only (1.8% of dose). In short, the unidirectional inversion of R‐ibuprofen appears to occur systemically rather than presystemically in dogs.