Simultaneous fitting of R‐ and S‐ibuprofen plasma concentrations after oral administration of the racemate

Aims  To assess the pharmacokinetic equivalence of two different formulations of ibuprofen lysinate with special focus on the expected effects.

Methods  Sixteen healthy volunteers received cross‐over ibuprofen lysinate as either one tablet of 400 mg (‘test’) or two tablets of 200 mg (‘reference’). Ibuprofen plasma concentrations were followed up for 10 h. Bioequivalence was assessed by standard noncompartmental methods. Ibuprofen plasma concentrations were fitted with a model that took bioinversion of R‐ to S‐ibuprofen into account.

Results  Peak plasma concentrations of R‐ and S‐ibuprofen were 18.1 and 20 µg ml⁻¹ (test), and 18.2 and 20 µg ml⁻¹ (reference). Areas under the plasma concentration vs time curves were 39.7 and 67.5 µg ml⁻¹ h (test), and 41.1 and 68.2 µg ml⁻¹ h (reference). Clearance of R‐ibuprofen was 5.2 (test) and 5 l h⁻¹ (reference). A specific plasma concentration was reached with the test formulation about 5 min later than with the reference. Parameters from compartmental modelling were (given for R‐and then for S‐ibuprofen): body clearance: 4.9 and 4.64 l h⁻¹, central volume of distribution: 2.8 and 4.1 l, intercompartment clearance: 5.1 and 5.45 l h⁻¹, peripheral volume of distribution: 4.1 and 5.2 l. The absorption rate constant was 1.52 h⁻¹, and the test but not the reference formulation had a lag time of 0.1 h. Simulations showed similarity between formulations of the expected effects except for a calculated delay of 6 min with the test formulation.

Conclusions  Ibuprofen formulations were bioequivalent. The pharmacokinetic model may serve as a basis for future pharmacokinetic/pharmacodynamic calculations after administration of racemic ibuprofen.

DOI: 10.1111/j.1365-2125.2001.01451.x

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