This study investigated the feasibility of using concurrent iv administration of
antipyrine (15 mg/kg
body weight) and bromosulphophthalein (BSP; 25 mg/kg) in the rat.
Antipyrine is used as an index of hepatic
drug metabolism and BSP is used to assess hepatic blood flow. Plasma concentrations of BSP were described using biexponential phases, while
antipyrine plasma concentrations were monoexponential. No significant difference was observed between
antipyrine pharmacokinetic parameters in concurrent BSP rats when compared with controls. There was also no significant difference between BSP pharmacokinetic parameters in concurrent
antipyrine rats when compared with controls, except in the alpha value (P less than 0.05). This indicates that BSP distribution may be affected by concurrent
antipyrine administration. Therefore, simultaneous administration of both substrates is not acceptable to study hepatic blood flow. Another iv combination dose (25 mg BSP/kg
body weight, followed by 15 mg
antipyrine/kg 0.5 hr later) and a dose of 15 mg
antipyrine/kg
body weight only was administered to rats pretreated with
phenobarbital (90 mg/kg
body weight) for 6 days. Pharmacokinetic parameters of BSP, beta, k21, k23 and plasma clearance, in the pretreated rats were significantly different from non-pretreated rats. No significant difference was observed in the pharmacokinetic parameters of
antipyrine between the combination dose and
antipyrine dose in the
phenobarbital-pretreated rats. The half-lives of
antipyrine in both pretreated groups decreased approximately by 70%, while the clearance increased four times compared with controls. The volume of distribution in these animals did not change as a result of
phenobarbital pretreatment. This suggests that a 25 mg BSP/kg
body weight dose followed by 15 mg
antipyrine/kg 0.5 hr later may be a feasible approach to study liver blood flow, as well as hepatic efficiency in rats.