Pharmacokinetics of PC-SOD, a Lecithinized Recombinant Superoxide Dismutase, After Single- and Multiple-Dose Administration to Healthy Japanese and Caucasian Volunteers
Open Access
- 1 February 2008
- journal article
- research article
- Published by Wiley in The Journal of Clinical Pharmacology
- Vol. 48 (2), 184-192
- https://doi.org/10.1177/0091270007309705
Abstract
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.Keywords
This publication has 20 references indexed in Scilit:
- SOD, oxidative stress and human pathologies: a brief history and a future visionBiomedicine & Pharmacotherapy, 2005
- Ischemia/reperfusion injury at the intersection with cell deathJournal of Molecular and Cellular Cardiology, 2005
- Overexpression of Human Copper/Zinc Superoxide Dismutase (SOD1) Suppresses Ischemia–Reperfusion Injury and Subsequent Development of Graft Coronary Artery Disease in Murine Cardiac GraftsCirculation, 2004
- Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and CardiotoxicityPublished by American Society for Pharmacology & Experimental Therapeutics (ASPET) ,2004
- Effects of lecithinized superoxide dismutase on neuronal cell loss in CA3 hippocampus after traumatic brain injury in ratsSurgical Neurology, 2003
- Lecithinized superoxide dismutase reduces cold ischemia-induced chronic allograft dysfunctionKidney International, 2002
- Status of myocardial antioxidants in ischemia–reperfusion injuryCardiovascular Research, 2000
- Targeted Disruption of the Mouse Sod I Gene Makes the Hearts Vulnerable to Ischemic Reperfusion InjuryCirculation Research, 2000
- Oxidants, Transcription Factors, and Intestinal InflammationJournal of Clinical Gastroenterology, 1997
- Role of Oxidants in Ischemic Brain DamageStroke, 1996