Bioavailability, food effect and tolerability of S-naproxen betainate sodium salt monohydrate in steady state.
S-Naproxen betainate sodium salt monohydrate (naproxen-beta Na, CAS 104124-26-7, Aprenin) in 550 mg capsules (corresponding to 327 mg of naproxen) was administered to 24 healthy volunteers (12 males and 12 females) b.i.d. to steady state in order to check its bioavailability, food interaction and tolerability. Plasma concentrations of naproxen were measured by a well validated HPLC method with fluorimetric detection as a morning pre-dose on days 1 to 6 and in timed samples in three different situations, as follows: a) after the morning dose on day 7 in a fasting status, b) after the evening dose and dinner on day 7 and c) after the morning dose of day 8, taken after a high-fat content breakfast. Pharmacokinetic parameters were evaluated from plasma concentrations by non-compartmental analysis to describe the above three situations. The steady state was reached early, namely by the second day of treatment. The extent of absorption did not differ in the three situations tested, whereas the rate of absorption was fastest in fasting conditions, lowest with the evening dose and intermediate after the high-fat content breakfast. The slow absorption rate of the evening dose was attributed to a circadian rhythm and should allow therapeutically active levels early in the morning, when arthritis pain is particularly tedious. In the three situations explored Cmax, Cmin and AUC were associated with CV % values ranging from 11.7 to 17.2%, which are very low and rare in pharmacokinetic trials. This low variability should allow an accurate estimate of the therapeutic effect expected. Tolerability was checked by objective and subjective symptoms, including vital signs, blood/urine biochemical parameters and occult blood in stools, and proved to be very good. From the comparison of these data with those previously published by other authors who have administered 500 mg of naproxen b.i.d., pre-dose concentrations in a steady state proved to be similar, despite the different doses administered, whereas Cmax and AUC obtained in this study were marginally lower. The kind of food interaction was the same as previously described in literature with naproxen.
Marzo
A
A
Institute for Pharmacokinetic and Analytical Studies (IPAS) S.A., Ligornetto, Switzerland.
Dal Bo
L
L
Wool
C
C
Cerutti
R
R
D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004041:Dietary Fats; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects* / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004041:Dietary Fats; D009288:Naproxen