Establishment of a bioassay to determine serum levels of dextran sulfate and pentosan polysulfate, two potent inhibitors of human immunodeficiency virus.
Dextran sulfate and pentosan polysulfate are two promising candidate anti-acquired immune deficiency syndrome (AIDS) drugs that have already been the subject of initial clinical trials in patients with AIDS. There is at present no reliable assay method to monitor blood drug levels in humans following the administration of either drug. We have now developed a sensitive bioassay system based on the inhibitory activity of the compounds against human immunodeficiency virus type 2 (HIV-2) in MT-4 cells. This method permits the detection in (rabbit) serum samples of dextran sulfate and pentosan polysulfate concentrations as low as 3.0 and 0.5 micrograms/ml, respectively. Pharmacokinetic studies with dextran sulfate and pentosan polysulfate in rabbits indicated that the half-life of these compounds after intravenous bolus injection is approximately 1 h 24 min.
Witvrouw
M
M
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Baba
M
M
Balzarini
J
J
Pauwels
R
R
De Clercq
E
E
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000818:Animals; D000998:Antiviral Agents / Q000097:blood* / Q000494:pharmacology; D001681:Biological Assay; D016264:Dextran Sulfate; D003911:Dextrans / Q000097:blood* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D009500:Neutralization Tests; D010426:Pentosan Sulfuric Polyester / Q000097:blood* / Q000494:pharmacology; D011134:Polysaccharides / Q000097:blood*; D011817:Rabbits; D014776:Virus Cultivation
D000998:Antiviral Agents; D003911:Dextrans; D011134:Polysaccharides; D010426:Pentosan Sulfuric Polyester; D016264:Dextran Sulfate