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Preliminary pharmacokinetic study of ibuprofen enantiomers after administration of a new oral formulation (ibuprofen arginine) to healthy male volunteers
Author(s) -
Fornasini Gianfranco,
Monti Nunzia,
Brogin Giandomenico,
Gallina Maddalena,
Eandi Mario,
Persiani Stefano,
Bani Massimo,
Pepa Carlo Della,
Zara Gianpaolo,
Benedetti Margherita Strolin
Publication year - 1997
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1997)9:3<297::aid-chir16>3.0.co;2-i
Subject(s) - ibuprofen , chemistry , enantiomer , pharmacokinetics , pharmacology , arginine , oral administration , chromatography , stereochemistry , biochemistry , amino acid , medicine
The pharmacokinetics of ibuprofen enantiomers were investigated in a crossover study in which seven healthy male volunteers received single oral doses of 800 mg racemic ibuprofen as a soluble granular formulation (sachet) containing L‐arginine (designated trade name: Spedifen®), 400 mg (‐)R‐ibuprofen arginine or 400 mg (+)S‐ibuprofen arginine. Plasma levels of both enantiomers were monitored up to 480 minutes after drug intake using an enantioselective analytical method (HPLC with ultraviolet detection) with a quantitation limit of 0.25 mg/l. Substantial inter‐subject variability in the evaluated pharmacokinetic parameters was observed in the present study. After (+)S‐ibuprofen arginine, the following mean pharmacokinetic parameters ±SD were calculated for (+)S‐ibuprofen: t max 28.6 ± 28.4 min; C max 36.2 ± 7.7 mg/l; AUC 86.4 ± 14.9 mg · h/l; t½ 105.2 ± 20.4 min. After (‐)R‐ibuprofen arginine, the following mean pharmacokinetic parameters were calculated for (+)S‐ibuprofen and (‐)R‐ibuprofen, respectively: t max 90.0 ± 17.3 and 50.5 ± 20.5 min; C max 9.7 ± 3.0 and 35.3 ± 5.0 mg/l; AUC 47.0 ± 17.2 and 104.7 ± 27.7 mg · h/l; t ½ 148.1 ± 63.6 and 97.7 ± 23.3 min. After racemic ibuprofen arginine, the following mean pharmacokinetic parameters were calculated for (+)S‐ and (‐)R‐ibuprofen, respectively: t max 30.7 ± 29.1 and 22.9 ± 29.8 min.; C max 29.9 ± 5.6 and 25.6 ± 4.4 mg/l; AUC 105.1 ± 23.0 and 65.3 ± 15.0 mg · h/l; t ½ 136.6 ± 20.7 and 128.6 ± 45.0 min. T max values of S(+)‐ and (‐)R‐ibuprofen after a single dose of 400 mg of each enantiomer did not differ significantly from the corresponding parameters obtained after a single dose of 800 mg of racemic ibuprofen arginine, indicating that the absorption rate of (‐)R‐ and (+)S‐ibuprofen is not different when the two enantiomers are administered alone or as a racemic compound. An average of 49.3 ± 9.0% of a dose of the (‐)R‐ibuprofen arginine was bioinverted into its antipode during the study period (480 minutes post‐dosing). The percent bioinversion during the first 30 minutes after (‐)R‐ibuprofen arginine intake averaged 8.1 ± 3.9%. The mean AUC of (+)S‐ibuprofen calculated after 800 mg racemic ibuprofen arginine (105.1 ± 23.0 mg · h/l) was lower than the mean AUC value obtained by summing the AUCs of (+)S‐ibuprofen after administration of 400 mg (+)S‐ibuprofen arginine and 400 mg (‐)R‐ibuprofen arginine (133.4 ± 26.6 mg · h/l). In conclusion, the administration of Spedifen® resulted in very rapid absorption of the (+)S‐isomer (eutomer) with t max values much lower than those observed for this isomer when conventional oral solid formulations such as capsules or tablets of racemic ibuprofen are administered. This characteristic is particularly favourable in those conditions in which a very rapid analgesic effect is required. Chirality 9:297–302, 1997. © 1997 Wiley‐Liss, Inc.