Pharmacokinetic study on a new antiischaemic agent (BRLP-42).

In the present study the pharmacokinetics of BRLP-42--a new antiischaemic agent--was investigated in dogs and rats. Plasma concentrations were measured by HPLC. After intravenous application the curves can be characterized by a two-compartment open pharmacokinetic model. The central volume of distribution (Vcentr.) is large (1.07 +/- 0.14 l/kg in dogs and 2.74 l/kg in rats), the first elimination half-life (t1/2 alpha) is 5.47 +/- 1.67 min in dogs and 13.7 min in rats. These facts indicate rapid and large tissue distribution. The excretion and/or metabolic elimination of BRLP-42 resulted in short second elimination half-life (t1/2 beta = 41.45 +/- 2.34 min in dogs and 43.8 min in rats). After oral application high individual variability can be seen. This fact may be due to the different rate and/or extent of absorption process. The plasma level curves can be characterized by a one-compartment open pharmacokinetic model. The absorption seems to conceal the distribution phase of the kinetic curve. The absorption half-life was short (t1/2a = 17.36 +/- 5.90 min in dogs and 2.7 min in rats). The bioavailability was 40 +/- 8% in dogs and 28% in rats. The elimination half-life (t1/2e = 28.77 +/- 0.88 min in dogs and 30.1 min in rats) is connected dominantly with metabolic elimination and/or excretion of BRLP-42. In the cases of intravenous as well as oral administrations the plasma concentrations decreased under the limit of quantitation by 4-6 hours in dogs and 4 hours in rats after treatments.