Pharmacokinetics of PC-SOD, a lecithinized recombinant superoxide dismutase, after single- and multiple-dose administration to healthy Japanese and Caucasian volunteers.
To study the pharmacokinetics of single increasing intravenous doses (40-160 mg) and repeated doses (80 mg for 7 days) of lecithinized superoxide dismutase (PC-SOD) in Japanese volunteers and to compare the pharmacokinetics of PC-SOD between Caucasians and Japanese. The Japanese study consisted of 2 parts: a single-dose, open-label, dose-escalation part and a multiple-dose, single-blind, placebo-controlled part. The pharmacokinetics of PC-SOD were determined using noncompartmental and compartmental methods. Pharmacokinetic data from a study with PC-SOD in Caucasians were reanalyzed using the same methodology. The mean (SD) terminal half-life of PC-SOD in Japanese subjects was 25 (4) hours for the 40-mg and 80-mg doses and 31 (15) hours for the 160-mg dose. There was nonlinearity between dose-normalized C(max) and clearance (P values .002 and .022). After multiple dosing, steady state was reached after 5 days. The observed accumulation ratio was 2.6 (0.5). The pharmacokinetics of the single 80-mg dose were similar for Japanese and Caucasians. The pharmacokinetics of PC-SOD was shown to be nonlinear with dose, which may be attributable to a saturable clearing mechanism. The relatively long half-life of PC-SOD (>24 hours) suggests that it is worthwhile to study the compound as a protective agent in clinical conditions with free radical overload.
Suzuki
Jun
J
R&D Division, LTT Bio-Pharma Co, Ltd, Tokyo 105-6201, Japan.
Broeyer
Freerk
F
Cohen
Adam
A
Takebe
Masato
M
Burggraaf
Jacobus
J
Mizushima
Yutaka
Y
D019540:Area Under Curve; D044466:Asian People; D015331:Cohort Studies; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016037:Single-Blind Method; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors; D044465:White People
D010713:Phosphatidylcholines; D013482:Superoxide Dismutase; C434045:lecithinized superoxide dismutase