INFLUENCE OF PERMANENT CANNULATION OF THE JUGULAR-VEIN ON PHARMACOKINETICS OF AMOXICILLIN AND ANTIPYRINE IN THE RAT

The effect of chronic cannulation of the rat jugular vein on the pharmacokinetics of amoxycillin and antipyrine administered by the i.v. and oral routes has been evaluated. Animals that received the i.v. dose of amoxycillin on the eighth day after jugular vein cannulation showed decreased clearance (4.0 +/- 0.3 ml/min) and steady-state volume of distribution (105 +/- 8 ml) compared to animals that received the i.v. dose on the fourth day (5.5 +/- 1.1 ml/min and 155 +/- 17 ml, respectively). Rats first dosed by the i.v. route showed an oral bioavailability of 54 +/- 12%, whereas for those first dosed by the oral route the calculated bioavailability was 31 +/- 6%. Antipyrine was administered to rats by the iv. and oral routes on the first and fourth days after jugular vein cannulation. Animals intravenously dosed on the fourth day showed a decreased clearance (1.9 +/- 0.3 ml/min) compared to rats intravenously dosed on the 1st day (2.7 +/- 0.6 ml/min). Antipyrine bioavailability was larger in animals first dosed by the i.v. route than in animals first dosed by the oral route (173 +/- 43 and 74 +/- 15%, respectively). These results argue against the use of crossover studies in rats with permanently implanted cannulas since kinetic changes induced by cannulation can be larger than previously proposed.