Pharmacokinetics of 8-phenyltheophylline in the rat

The pharmacokinetics of the adenosine antagonist 8-phenyltheophylline (8-PT) have been investigated in the rat. After intravenous administration to male rats with normal renal function, 8-PT was rapidly cleared from plasma with a t1/2 of about 14 min. Its apparent volume of distribution was some 76 mL/100 g and plasma clearance was 3.5 mL min-1/100 g. Injection via the carotid artery did not alter the kinetics of 8-PT, but when given through the portal vein a first-pass effect was observed. Moreover, 8-PT could not be detected in plasma following intraperitoneal injection. The kinetics of 8-PT were not altered in male rats with acute renal failure and no difference was noted between male and female animals with respect to the kinetics of 8-PT following intravenous injection. It is concluded that the pharmacokinetic properties of 8-PT are likely to complicate its use in-vivo.