Steady state pharmacokinetics of tiaprofenic acid in elderly patients

Tiaprofenic acid (Surgam) steady state pharmacokinetics was investigated in eight elderly patients with three different dosage regimens: 200 mg twice daily, 400 mg twice daily and 200 mg three times daily. The following dose independent pharmacokinetic parameters were evaluated from a two-compartment open model; absorption lag time: 0.23 +/- 0.08 h, absorption rate constant: 4.32 +/- 0.51 h-1, distribution rate constant: 1.31 +/- 0.13 h-1 and elimination half-life: 4.66 +/- 0.42. An increase in dose produced a significant and proportional increase in tiaprofenic acid peak and trough serum concentrations at steady state. In contrast to the above mentioned dose independent parameters, the area under the serum concentration-time curve showed a small (12%), but significantly higher increase than expected when the dosage regimen was increased from 200 mg X 2 to 400 mg X 2. This was, however, considered to be of no clinical relevance. Anticipating a 19% reduction of tiaprofenic acid bioavailability due to the intake of food, approximations of total body clearance and apparent volume of distribution can be made to 30.0 +/- 2.0 ml/min and 11.8 +/- 2.0 l, respectively. In spite of the small disproportional increase (12%) observed in the area under the serum concentration-time curve, it can be concluded that tiaprofenic acid shows a well defined pharmacokinetics in old people with acceptable interindividual variations and with a fast building-up to constant and predictable steady state levels within the dosage regimens investigated. A linear relationship was demonstrated between creatinine clearance and tiaprofenic acid total body clearance.(ABSTRACT TRUNCATED AT 250 WORDS)