Pharmacokinetic Studies on Hematoporphyrin Monomethyl Ether: A New Promising Drug for Photodynamic Therapy of Tumors

Objective To study the pharmacokinetic rule of hematoporphyrin monomethyl ether(HMME) in animal after intravenous injection. Methods Fifteen rabbits were randomly and equally divided into 3 groups. The tested rabbits were injected intravenously with 10, 20 or 40 mg/kg of HMME, respectively. The plasma concentration of HMME in rabbits after intravenous injection was determined by fluorospectrophotometry. The excitation and emission wavelengths were 395 and 613 nm, respectively. The pharmacokinetic parameters of HMME in rabbits were calculated by computer according to the plasma cocentration time data. Results The average recovery of HMME from plasma was 97 20% (CV=2 19%), 97 30%(CV=2 26%) and 98 60 (CV=2 03%) at concentration of 10, 20 and 40 μg/ml, respectively. It was indicated that the pharmacokinetics of HMME in rabbits after intravenous injection was fit for a three compartment open model. The principal pharmacokinetic parameters were T 1/2π =3.051 min, T 1/2α =15.77 min, T 1/2β =149.84 min, Vc=0.757 L/kg, Cl=0.065 2 L·kg -1 ·min -1 , AUC=153 μg·min -1 ·ml -1 (10 mg/kg); T 1/2π =1.845 min, T 1/2α =20.46 min, T 1/2β =159.71 min, Vc=0.074 L/kg, Cl=0.020 0 L·kg -1 ·min -1 , AUC=998 μg·min -1 ·ml -1 (20 mg/kg); T 1/2π =2.617 min, T 1/2α =21.57 min, T 1/2β =353.01 min, Vc=0.040 L/kg, Cl=0.008 4 L·kg -1 ·min -1 , AUC=4 764 μg·min -1 ·ml -1 (40 mg/kg), respectively. Conclusions It was suggested that the plasma concentration time course of HMME in rabbits after intravenous injection was a first order linear kinetic process. The data of the first distribution phase and the second distribution phase showed that HMME was distributed rapidly to the peripheral compartment from the central compartment in rabbits after intravenous injection. The data of the elimination phase showed that HMME was eliminated more quickly and was not accumulated, thus significantly reducing the systematic side effects.