Abstract:

Objective: To compare the bioavailability parameter values of ibuprofen 600mg or codeine 30mg when administered in a new combined solid oral formulation versus each agent administered alone.

Design: Non-blind, comparative, crossover, three-way (ibuprofen, codeine, ibuprofen plus codeine) randomised clinical trial.

Setting: Phase 1 study unit.

Subjects: 24 healthy volunteers of both genders (12 males and 12 females) with the following average characteristics: age 22.6 years; bodyweight 63.2kg; height 171cm; body mass index 21.47 kg/m.

Interventions: During each study period, a single oral dose of one of the formulations was administered, and 13 plasma samples were obtained to determine drug concentrations and calculate pharamcokinetic parameter values.

Results: The pharmacokinetic parameter values [mean ± standard deviation, except median for time to maximum plasma concentration (t)] calculated for each drug and formulation were as follows: For ibuprofen (combined with codeine) versus ibuprofen alone: area under the concentration-time curve from time zero to infinity (AUC), 202.06 ± 43.62 vs 204.19 ± 52.79 mg•h/L; maximum plasma concentration (C), 64.93 ± 11.91 vs 57.01 ± 15.47 mg/L; t, 1.00 vs 1.50h. The 90% confidence intervals (CI) of the ratios (%) of logarithmically transformed values were: AUC 95.88 to 104.22; C 104.75 to 129.63; the CI (Wilcoxon test) of the median difference in t was -0.80 to -0.13h. For codeine (combined with ibuprofen) versus codeine alone: AUC 417.82 ± 115.55 vs 354.36 ± 114.43 g•h/L; C 115.12 ± 38.85 vs 89.05 ± 27.09 g/L; t 1.00 vs 1.00h. The CI of the ratios (%) of logarithmically transformed values were: AUC 111.84 to 126.18; C 116.66 to 139.57; the CI (Wilcoxon test) of the median difference in t was -0.25 to 0.17h.

Conclusions: The rate and extent of ibuprofen release/absorption from both formulations are within bioequivalence limits. The extent of absorption of codeine is slightly greater from the combination form, with a similar rate of release/absorption. The slight differences found are attributable to the galenic formulations. These results confirm the good bioavailability of ibuprofen and codeine from the new formulation, and exclude any impairment of absorption when the drugs are formulated in combination.

Keywords: Analgesics, pharmacokinetics; Codeine, pharmacokinetics; Ibuprofen, pharmacokinetics; Ibuprofen/codeine, pharmacokinetics; Nonsteroidal anti inflammatories, pharmacokinetics

Language: English

Document Type: Original article

Affiliations: 1: Unidad de Estudios de Farmacología Clínica, Servicio de Farmacología Clínica, Hospital Clínico San Carlos, Madrid, Spain 2: Laboratorios Knoll, SA, Madrid, Spain 3: MCC Analítica, Barcelona, Spain *