In vivo recovery and survival of monoclonal-antibody-purified factor VIII concentrates.
In response to reports of discrepant in vitro assays of high-purity concentrates, a double-blind crossover study of in vivo recovery and half-life of two brands of monoclonal-antibody-purified factor VIII concentrates (Monoclate and Hemofil-M) was performed in 23 patients with hemophilia A. In vivo recoveries were close to values predicted from the labelled unitage when plasma samples were assayed by a one-stage method. When a two-stage assay was used, lower recoveries were calculated and the recovery with Hemofil-M was slightly but significantly lower than that with Monoclate. The concentrates were re-assayed in vitro by the two-stage method. Monoclate (which is assayed by the manufacturer using a two-stage method) contained 97% of the labelled potency and Hemofil-M (which is assayed by the manufacturer using a one-stage method) contained 81% of the labelled potency. Differences in in vitro and in vivo assay methods contribute to disparities between expected and observed factor VIII recovery. Clearance of Hemofil-M was significantly faster than that of Monoclate, but volume of distribution at the steady state, mean residence time, and plasma half-disappearance times of the two concentrates were not significantly different.
Kasper
C K
CK
Department of Medicine, University of Southern California, Los Angeles.
Kim
H C
HC
Gomperts
E D
ED
Smith
K J
KJ
Salzman
P M
PM
Tipping
D
D
Miller
R
R
Montgomery
R M
RM
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D002648:Child; D004311:Double-Blind Method; D005169:Factor VIII / Q000302:isolation & purification / Q000493:pharmacokinetics*; D006207:Half-Life; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D005169:Factor VIII