Pharmacokinetics of fosfosal after single and multiple oral doses in man

Int J Clin Pharmacol Ther Toxicol. 1988 Sep;26(9):421-7.

Abstract

Fosfosal is a new salicylic acid derivative used in analgesic and anti-inflammatory therapy. In this study, pharmacokinetic evaluation of fosfosal after a single 2,400 mg and three different oral dose schedules (1,200 mg t.i.d., 2,400 mg b.i.d. and 2,400 mg t.i.d.) was carried out, in six healthy male volunteers, to assess which doses provide steady state plasma concentrations within the therapeutic range (150-300 micrograms/ml). Plasma concentrations of both fosfosal and its active metabolite, salicylic acid, were determined by means of an HPLC method. For the 2,400 mg t.i.d., Cmin-ss and Cmax-ss values were 184 micrograms/ml and 276 micrograms/ml, respectively, being significantly higher (p less than 0.02) than with the other regimes and, unlike the latter, falling within the anti-inflammatory therapeutic range. In addition, the 2,400 mg t.i.d. showed a significant prolongation (p less than 0.005) of salicylic acid t1/2, as well as a higher AUC-ss 0-8 h dosing interval compared to the other multidose schedules and to the AUC0-infinity for the single dose. As expected, both facts reflect that the highest daily dose of fosfosal has a nonlinear concentration-dependent elimination rate.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / blood
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Drug Administration Schedule
  • Humans
  • Male
  • Organophosphates / administration & dosage
  • Organophosphates / blood
  • Organophosphates / pharmacokinetics*
  • Organophosphorus Compounds / pharmacokinetics*
  • Salicylates / blood

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Organophosphates
  • Organophosphorus Compounds
  • Salicylates
  • fosfosal