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Pharmacokinetics of PC‐SOD, a Lecithinized Recombinant Superoxide Dismutase, After Single‐ and Multiple‐Dose Administration to Healthy Japanese and Caucasian Volunteers
Author(s) -
Suzuki Jun,
Broeyer Freerk,
Cohen Adam,
Takebe Masato,
Burggraaf Jacobus,
Mizushima Yutaka
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007309705
Subject(s) - pharmacokinetics , pharmacology , superoxide dismutase , placebo , medicine , dosing , half life , oxidative stress , pathology , alternative medicine
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, singleblind, 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.