Pharmacokinetics of pyronaridine in malaria patients
Feng, Z.; Wu, Z.F.; Wang, C.Y.; Jiang, N.X.
Zhongguo Yao Li Xue Bao 8(6): 543-546
1987
ISSN/ISBN: 0253-9756 PMID: 3330403 Document Number: 293291
Pyronaridine (PND), an antimalarial, was first developed in China. Its chemical name is 2-methoxy-7-chloro-10--1,5-naphthyridine tetraphospahte. Its pharmacokinetics after im and po to malaria (Plasmodium falciparum and P. vivax) patients were studied. The whole blood concentrations were measured periodically for 72 h, using a sensitive and specific spectrofluorometric method. The concentration-time data were analyzed with a modified NONLIN computer program on IBM-PC microcomputer. Four patients were given a single dose (204 mg) im, and the concentration-time course was adequately fitted to a linear 2-compartment open model. There were considerable variations in the estimated kinetic parameters, but the differences did not appear to be related to the dosage. It was rapidly absorbed with a mean Cmax of 525 ng/ml at Tmax 0.66 h. The T11/2.beta. was 63 .+-. 5 h. The mean Vc and Vss were 11.1 and 71.5 L/kg, respectively indicating an extensive tissue distribution. After a single oral dose of 0.6 g PND in enteric-coated tablets (3 patients) or in capsules (3 patients), the T1/2.beta. were 65 .+-. 6 and 63 .+-. 6 h; mean Tmax, 14.0 and 4.7 h; Cmax, 127.5 and 255.3 ng/ml, respectively. In comparison with im, oral PND was much less bioavailable. The relative extents of absorption for tablets and capsules were found to be 19 .+-. 7 and 32 .+-. 7%, respectively. It was shown that PND oral formulation in current use should be improved to increase its bioavailability.