A comparative pharmacokinetic study of recombinant human serum albumin with plasma-derived human serum albumin in patients with liver cirrhosis.
We conducted an open-label, parallel-group study of the high purity, mass-produced recombinant human serum albumin (rHSA), derived from the methylotrophic yeast Pichia pastoris, to compare pharmacokinetics and ensure bioequivalence with plasma-derived human serum albumin (pHSA) in 22 patients with liver cirrhosis. Both rHSA and pHSA groups enrolled 11 patients each, assigned according to predose serum albumin concentrations using the minimization method. Pharmacokinetic and safety profiles for 3-day repeated intravenous infusions at a daily dose of 25 g were evaluated for 8 days. Geometric mean AUC(0-168hr) (g.hr/dL) was 637.12 and 635.93 in the rHSA and pHSA groups, respectively, with a 90% confidence interval (CI) for the difference (92.9%-108.1%) lying within the bioequivalence range. The other major parameter, geometric mean C(max) (g/dL), was 4.16 and 4.19 in the rHSA and pHSA groups, respectively, with a 90% CI for the difference (92.7%-106.4%). The pHSA group presented with 3 adverse events: 1 case of insomnia, and 2 laboratory abnormalities with no serious adverse events. Results from this study show similar pharmacokinetic profiles following intravenous administration of 25g/day of rHSA and pHSA for 3 days, indicating bioequivalence.
Ohnishi
Kunihiko
K
Ohnishi Hospital, Saitama, Japan.
Kawaguchi
Atsuhiro
A
Nakajima
Shunji
S
Mori
Hiroyuki
H
Ueshima
Takahiro
T
D000368:Aged; D019540:Area Under Curve; D001663:Bilirubin / Q000097:blood; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D005260:Female; D006207:Half-Life; D006801:Humans; D007260:Infusion Pumps; D007275:Injections, Intravenous; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010843:Pichia / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012709:Serum Albumin / Q000009:adverse effects / Q000235:genetics / Q000493:pharmacokinetics*; D012737:Sex Factors; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D013810:Therapeutic Equivalency
D011994:Recombinant Proteins; D012709:Serum Albumin; D003404:Creatinine; D001663:Bilirubin